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1

Sunal, R., I. Kanzik, and N. Abacioglu. "Antidepressant-like activity of cimetidine." Behavioural Brain Research 16, no. 2-3 (August 1985): 231. http://dx.doi.org/10.1016/0166-4328(85)90152-4.

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Kalra, BhupinderSingh, Vandana Tayal, and Shalini Chawla. "Antidepressant-like activity of tramadol in mice." Indian Journal of Psychiatry 50, no. 1 (2008): 51. http://dx.doi.org/10.4103/0019-5545.39760.

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Tomonaga, Shozo, Haruka Yamane, Eiichiro Onitsuka, Satoshi Yamada, Mikako Sato, Yoshihisa Takahata, Fumiki Morimatsu, and Mitsuhiro Furuse. "Carnosine-induced antidepressant-like activity in rats." Pharmacology Biochemistry and Behavior 89, no. 4 (June 2008): 627–32. http://dx.doi.org/10.1016/j.pbb.2008.02.021.

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4

Wierońska, Joanna M., Piotr Brański, Agnieszka Pałucha-Poniewiera, and Andrzej Pilc. "Antidepressant-like activity of metabotropic glutamate receptors." Pharmacological Reports 62 (September 2010): 23–24. http://dx.doi.org/10.1016/s1734-1140(10)71114-2.

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5

Vasileva, E., A. Abdullina, E. Kondrakhin, and G. Kovalev. "Antidepressant-like activity of cyclo-l-prolylglycine." European Neuropsychopharmacology 29 (2019): S544—S545. http://dx.doi.org/10.1016/j.euroneuro.2018.11.804.

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6

Hsu, Lieh-Ching, Yu-Jen Ko, Hao-Yuan Cheng, Ching-Wen Chang, Yu-Chin Lin, Ying-Hui Cheng, Ming-Tsuen Hsieh, and Wen Huang Peng. "Antidepressant-Like Activity of the Ethanolic Extract fromUncaria lanosaWallich var.appendiculataRidsd in the Forced Swimming Test and in the Tail Suspension Test in Mice." Evidence-Based Complementary and Alternative Medicine 2012 (2012): 1–12. http://dx.doi.org/10.1155/2012/497302.

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This study investigated the antidepressant activity of ethanolic extract ofU. lanosaWallich var.appendiculataRidsd (ULEtOH) for two-weeks administrations by using FST and TST on mice. In order to understand the probable mechanism of antidepressant-like activity of ULEtOHin FST and TST, the researchers measured the levels of monoamines and monoamine oxidase activities in mice brain, and combined the antidepressant drugs (fluoxetine, imipramine, maprotiline, clorgyline, bupropion and ketanserin). Lastly, the researchers analyzed the content of RHY in the ULEtOH. The results showed that ULEtOHexhibited antidepressant-like activity in FST and TST in mice. ULEtOHincreased the levels of 5-HT and 5-HIAA in cortex, striatum, hippocampus, and hypothalamus, the levels of NE and MHPG in cortex and hippocampus, the level of NE in striatum, and the level of DOPAC in striatum. Two-week injection of IMI, CLO, FLU and KET enhanced the antidepressant-like activity of ULEtOH. ULEtOHinhibited the activity of MAO-A. The amount of RHY in ULEtOHwas 17.12 mg/g extract. Our findings support the view that ULEtOHexerts antidepressant-like activity. The antidepressant-like mechanism of ULEtOHmay be related to the increase in monoamines levels in the hippocampus, cortex, striatum, and hypothalamus of mice.
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Zayka, Tamara O., Dmitriy V. Evdokimov, Yulia V. Sidorova, Igor I. Abramets, and Sergey V. Nalotov. "Antidepressant-like effects of substances with cerebroprotective activity." Biological Markers and Guided Therapy 2 (2015): 79–88. http://dx.doi.org/10.12988/bmgt.2015.5117.

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8

Jain, Harshita, Prateek Jain, Bharti Ahirwar, and Dheeraj Ahirwar. "ANTIDEPRESSANT ACTIVITY OF THYMOQUINONE POSSIBLY THROUGH INVOLVEMENT OF CORTICOTROPIN RELEASING FACTOR." Asian Journal of Pharmaceutical and Clinical Research 10, no. 11 (November 1, 2017): 392. http://dx.doi.org/10.22159/ajpcr.2017.v10i11.21773.

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Objective: Present study aimed to evaluate the antidepressant-like activity of thymoquinone (TQ) in unstressed and stressed condition and to explore the possible underlying mechanism for this activity.Methods: TQ (5, 10, and 20 mg/kg) and fluoxetine per se were administered to the unstressed and stressed mice; immobility periods were observed using forced swim test (FST) and tail suspension test (TST). Effect of corticotropin-releasing factor (CRF)-1 antagonist on antidepressant-like activity was also evaluated. The mechanism of action was also explored by measuring plasma corticosterone levels.Results: TQ (20 mg/kg) and fluoxetine per se significantly decreased immobility periods in stressed mice indicating significant antidepressant-like activity under stress. There was no significant effect on locomotor activity of the mice on treatment with TQ and fluoxetine per se. It significantly decreased plasma corticosterone level. Antalarmin (a CRF-1 receptor antagonist) significantly attenuated TQ induced the antidepressant-like effect in both FST and TST.Conclusion: TQ significantly produced antidepressant-like activity in mice possi‑bly through inhibiting CRF activity and decreasing plasma corticosterone levels.
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9

Reis, Elizete De Moraes, Francisco Waldomiro Schreiner Neto, Vitória Berg Cattani, Luis Ricardo Peroza, Alcindo Busanello, Caroline Queiroz Leal, Aline Augusti Boligon, et al. "Antidepressant-Like Effect ofIlex paraguariensisin Rats." BioMed Research International 2014 (2014): 1–9. http://dx.doi.org/10.1155/2014/958209.

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In this study, we investigated the possible antidepressant-like effect ofI. paraguariensisin rats. Rats were treated for four weeks with an aqueous extract ofI. paraguariensisin drinking water, following the traditional preparation of this beverage. After the period of treatment, behavioral (elevated plus-maze, open field test, and forced swimming test) and biochemical parameters (lipid peroxidation assay, thiol content, vitamin C levels, and monoamine oxidase activity) were evaluated. Animals were also analyzed on forced swimming test after 24 hours ofI. paraguariensisintake. An additional group was injected with selegiline 24 hours and 30 minutes before forced swimming test as positive control. HPLC analysis revealed the profile ofI. paraguariensisextract.I. paraguariensisreduced the immobility time on forced swimming test without significant changes in locomotor activity in the open field test. Any anxiolytic/anxiogenic effect ofI. paraguariensiswas observed in rats through the elevated plus-maze test. The antidepressant-like effect ofI. paraguariensiswas not accompanied by inhibitory effect on monoamine oxidase activity. There were no significant alterations on lipid peroxidation, thiol content, and vitamin C levels among the groups. In conclusion, aqueous extract ofI. paraguariensisdecreases the time of immobility in rats suggesting an antidepressant-like effect.
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10

Estrada-Reyes, Rosa, Daniel B. Quero-Chávez, Citlali Trueta, Armida Miranda, Marcela Valdés-Tovar, Salvador Alarcón-Elizalde, Julián Oikawa-Sala, et al. "Low Doses of Ketamine and Melatonin in Combination Produce Additive Antidepressant-like Effects in Mice." International Journal of Molecular Sciences 22, no. 17 (August 26, 2021): 9225. http://dx.doi.org/10.3390/ijms22179225.

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Major depressive disorder is a disabling disease with the number of affected individuals increasing each year. Current antidepressant treatments take between three to six weeks to be effective with forty percent of patients being resistant to treatment, making it necessary to search for new antidepressant treatments. Ketamine, a phencyclidine hydrochloride derivative, given intravenously, induces a rapid antidepressant effect in humans. In mice, it causes increased neurogenesis and antidepressant-like effects. However, it also produces psychomimetic effects in humans and in rodents increases the locomotor activity. In contrast, melatonin, a hormone secreted by the pineal gland and synthesized in extrapineal sites, increases new neuron formation and causes antidepressant-like effects in adult rodents with no collateral effects. Here, we assessed the effects of a non-effective dose of ketamine in combination with melatonin (KET/MEL), both on neurogenesis as well as on the antidepressant-like effect in mice. Our results showed that KET/MEL combination increased neurogenesis and produced antidepressant-like effects without altering locomotor activity after both single and triple administration protocols. Our data strongly suggest that KET/MEL combination could be used to simultaneously promote neurogenesis, reverting neuronal atrophy and inducing antidepressant-like effects.
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11

Chenu, Franck, and Michel Bourin. "Potentiation of Antidepressant-Like Activity with Lithium: Mechanism Involved." Current Drug Targets 7, no. 2 (February 1, 2006): 159–63. http://dx.doi.org/10.2174/138945006775515392.

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12

Wei-Jun. "Antidepressant-Like Activity of Banana Peel Extract in Mice." American Medical Journal 2, no. 2 (October 1, 2011): 59–64. http://dx.doi.org/10.3844/amjsp.2011.59.64.

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13

Gordon, M. "Oral Versus Transdermal Selegiline Antidepressant-Like Activity in Rats." Pharmacology Biochemistry and Behavior 63, no. 3 (July 1999): 501–6. http://dx.doi.org/10.1016/s0091-3057(99)00016-7.

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14

Covington, Herbert E., Vincent F. Vialou, Quincey LaPlant, Yoshinori N. Ohnishi, and Eric J. Nestler. "Hippocampal-dependent antidepressant-like activity of histone deacetylase inhibition." Neuroscience Letters 493, no. 3 (April 2011): 122–26. http://dx.doi.org/10.1016/j.neulet.2011.02.022.

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15

Poleszak, Ewa, Bernadeta Szewczyk, Ewa Kędzierska, Piotr Wlaź, Andrzej Pilc, and Gabriel Nowak. "Antidepressant- and anxiolytic-like activity of magnesium in mice." Pharmacology Biochemistry and Behavior 78, no. 1 (May 2004): 7–12. http://dx.doi.org/10.1016/j.pbb.2004.01.006.

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16

Dhingra, Dinesh, and Amandeep Sharma. "Evaluation of antidepressant-like activity of glycyrrhizin in mice." Indian Journal of Pharmacology 37, no. 6 (2005): 390. http://dx.doi.org/10.4103/0253-7613.19077.

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17

Perveen, Shahnaz, Arfa Yasmeen, Muhammad Khan, Ahsana Dar, Rehana Jafri, and Amir Ahmed. "Structure Activity Relationship of Organic Alcohol and Esters for Antidepressant- Like Activity." Letters in Drug Design & Discovery 7, no. 1 (January 1, 2010): 14–17. http://dx.doi.org/10.2174/157018010789869334.

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18

Babu, Dr Kuppala Manohar, Pandrinki Geetha Mounika, Rakurthi J. S. D. Pawan kumar, Nunna Priyanka, and Ayasetti Durga Sravani. "Evaluation of Antidepressant Activity of Plocama pendula root extract." Caribbean Journal of Science and Technology 08, no. 01 (2020): 25–35. http://dx.doi.org/10.55434/cbi.2020.8102.

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Plocama is a flowering plant genus belonging to Rubiaceae family. The natural products are soxlated from the dried powder of Plocama root with various solvents like n-Hexane, Ethyl acetate, Chloroform, Water and Ethanol. Phytochemical screening revealed that Alkaloids are present in chloroform extract whereas Anthocyanins are present in ethanol extract. Terpenoids, Flavonoids, Alkaloids and Phenolic compounds are present in water extract. In the present study, Plocama pendula root water extract (PPRWE) (400 mg/kg) produced significant antidepressant effect in Forced swim test & Tail Suspension Test. Ecliptin alkaloid & Culumbin, a flavonoid present in PPRWE may be facilitating monoaminergic transmission there by producing antidepressant effects. In this work, it was demonstrated that the administration of different doses of the water extract of Plocama pendula root in mice was able to induce antidepressant effects. On the basis of the clinical association of depressive episodes and stressful life events, many of the animal models for the evaluation of antidepressant drug activity assess stress‐precipitated behaviors. Results of this study showed that the administration of the PPRWE produced a diminution of immobility time of mice exposed to the both forced swimming and tail suspension tests. Harmaline alkaloidspresent in Plocama pendulaact as reversible monoamine oxidase inhibitors and in common with other beta carboline binds to 5‐Hydroxy Tryptamine receptors. Inhibition of this enzyme causes a reduction in metabolism and subsequent increase in the concentration of biogenic amines. The flavonoid components of PPRWE might be interacting with adrenergic and serotonergic systems in mediating the antidepressant effects of PPRWE. However, the precise mechanisms by which the extract produced antidepressant‐like effect are not completely understood. Further studies would be necessary to evaluate the contribution of active chemical constituents for the observed antidepressant activity.
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19

Abdelwahab, SiddigIbrahim, Hassan Alfaifi, Syam Mohan, ManalMohamed Elhassan Taha, SohierM Syame, LamiaaA Shaala, and Rashad Alsanosy. "Catha edulis Forsk. (Khat): Evaluation of its antidepressant-like Activity." Pharmacognosy Magazine 13, no. 50 (2017): 354. http://dx.doi.org/10.4103/pm.pm_442_16.

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20

Dhingra, Dinesh, and Sudha Bansal. "Antidepressant-like activity of plumbagin in unstressed and stressed mice." Pharmacological Reports 67, no. 5 (October 2015): 1024–32. http://dx.doi.org/10.1016/j.pharep.2015.03.001.

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21

Socolsky, Cecilia, Stela M. K. Rates, Ana Cristina Stein, Yoshinori Asakawa, and Alicia Bardón. "Acylphloroglucinols from Elaphoglossum crassipes: Antidepressant-like Activity of Crassipin A." Journal of Natural Products 75, no. 6 (June 11, 2012): 1007–17. http://dx.doi.org/10.1021/np200436h.

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22

Poleszak, E. "Modulation of antidepressant-like activity of magnesium by serotonergic system." Journal of Neural Transmission 114, no. 9 (April 20, 2007): 1129–34. http://dx.doi.org/10.1007/s00702-007-0714-8.

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23

Sowa-Kućma, Magdalena, Beata Legutko, Bernadeta Szewczyk, Kinga Novak, Paweł Znojek, Ewa Poleszak, Mariusz Papp, Andrzej Pilc, and Gabriel Nowak. "Antidepressant-like activity of zinc: further behavioral and molecular evidence." Journal of Neural Transmission 115, no. 12 (September 3, 2008): 1621–28. http://dx.doi.org/10.1007/s00702-008-0115-7.

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Yadavalli, Chandrasekhar, Phani Kumar Garlapati, and Anilakumar Kandangath Raghavan. "Gallic Acid from Terminalia Bellirica Fruit Exerts Antidepressant-like Activity." Revista Brasileira de Farmacognosia 30, no. 3 (May 21, 2020): 357–66. http://dx.doi.org/10.1007/s43450-020-00020-w.

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25

Huang, Chih-Chia, Mang-Hung Tsai, Ya-Chieh Wu, Kuang-Ti Chen, Han-Wen Chuang, Yun Chen, Guan-Woei Tseng, Pin-I. Fu, and I.-Hua Wei. "Activity Dependent Mammalian Target of Rapamycin Pathway and Brain Derived Neurotrophic Factor Release is Required for the Rapid Antidepressant Effects of Puerarin." American Journal of Chinese Medicine 46, no. 07 (January 2018): 1519–34. http://dx.doi.org/10.1142/s0192415x18500787.

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Puerarin is a traditional Chinese medicine with beneficial effects of reduced depression-like behaviors in mice with stress. Previous studies also show that puerarin can produce neuroprotective effect via activating the Akt or increased brain-derived neurotrophic factor (BDNF) expression. Interestingly, BDNF and Akt downstream target, mammalian target of rapamycin (mTOR) mediate the fast-acting antidepressant properties of ketamine. Until now, the involvement of the mTOR signaling pathway or BDNF on puerarin-induced antidepressant effect remains unknown. We aimed to investigate whether the antidepressant-like effect induced by puerarin would associate mTOR signaling pathway and BDNF release. The antidepressant-like effects of puerarin were evaluated using the forced swim test. The activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionaic acid receptor (AMPAR)-mTOR signaling pathway and release of BDNF in the prefrontal cortex were determined. We also investigated the effect of puerarin on AMPAR trafficking through measuring the PKA phosphorylation of AMPAR subunit GluR1. Our present results show that puerarin exerted antidepressant-like responses that was mediated by AMPAR-induced mTOR signaling pathway and associated with increased BDNF release. Moreover, a significant increase in the GluR1 phosphorylation at its PKA site was noted following puerarin treatment. Our findings are the first to demonstrate that the antidepressant-like actions of puerarin require AMPAR–mTOR signaling pathway activation, are associated with an increased BDNF level and facilitate AMPAR membrane insertion. These findings provide preclinical evidence that puerarin may possess antidepressant property which is mediated by the glutamatergic system.
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Sacchet, Cassia, Ricieri Mocelin, Adrieli Sachett, Fernanda Bevilaqua, Rafael Chitolina, Fernanda Kuhn, Aline Augusti Boligon, et al. "Antidepressant-Like and Antioxidant Effects ofPlinia trunciflorain Mice." Evidence-Based Complementary and Alternative Medicine 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/601503.

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The jaboticaba tree,Plinia trunciflora(O. Berg) Kausel, is popularly named “jabuticabeira” in Brazil and is used in folk medicine to treat diabetes and chronic inflammation of the tonsils, but studies evaluating the central effects of this species are limited. This study evaluated the antidepressant-like and antioxidant effects ofP. trunciflora(PT) aqueous extract, in which five different anthocyanins were identified. PT showed significant ferric-reduction power and DPPH radical scavenging activityin vitroand reduced lipid peroxidation bothin vitroandex vivo. At the behavioural level, PT (400 and 800 mg/kg, i.p.) dose-dependently reduced immobility time in the tail suspension test in Swiss male mice. The identification of bioactive compounds accompanied by thein vitroandex vivoantioxidant activity of PT suggests that these activities might be related to the antidepressant-like activity ofP. trunciflora.
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Es-safi, Imane, Hamza Mechchate, Amal Amaghnouje, Fatima Zahra Jawhari, Omkulthom Mohamed Al Kamaly, Hamada Imtara, Andriy Grafov, Amina Bari, and Dalila Bousta. "An Insight into the Anxiolytic and Antidepressant-Like Proprieties of Carum carvi L. and Their Association with Its Antioxidant Activity." Life 11, no. 3 (March 5, 2021): 207. http://dx.doi.org/10.3390/life11030207.

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Depression and anxiety are widespread illnesses whose consequences on patients’ social and professional lives are becoming ever more dangerous and severe. The study’s objective is to explore the antidepressant-like and anxiolytic activity of the polyphenolic extract of Carum carvi L. as well as its antioxidant power as they were recently associated. The predictive antidepressant activity was evaluated using the forced swimming and tail suspension test in mice, a preclinical behavioral model widely used to determine the efficacy of antidepressant drugs. As for anxiolytic-like activity, two models were used, namely the light/dark chamber test to measure the animal’s degree of anxiety and the open field test to evaluate both anxiolytic and locomotor activity. The tests results indicate a remarkable antidepressant and anxiolytic-like effect after oral administration of the polyphenolic fraction of C. carvi and interesting antioxidant property. In the extract it has been confirmed the presence of 6 molecules belonging to polyphenols, identified with HPLC analysis. This study confirms and encourages the traditional use of the extract and appeals to further studies to understand its action mechanism.
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Friedland, Kristina, Giacomo Silani, Anita Schuwald, Carola Stockburger, Egon Koch, Michael Nöldner, and Walter E. Müller. "Neurotrophic Properties of Silexan, an Essential Oil from the Flowers of Lavender-Preclinical Evidence for Antidepressant-Like Properties." Pharmacopsychiatry 54, no. 01 (November 30, 2020): 37–46. http://dx.doi.org/10.1055/a-1293-8585.

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Abstract Background Silexan, a special essential oil from flowering tops of lavandula angustifolia, is used to treat subsyndromal anxiety disorders. In a recent clinical trial, Silexan also showed antidepressant effects in patients suffering from mixed anxiety-depression (ICD-10 F41.2). Since preclinical data explaining antidepressant properties of Silexan are missing, we decided to investigate if Silexan also shows antidepressant-like effects in vitro as well as in vivo models. Methods We used the forced swimming test (FST) in rats as a simple behavioral test indicative of antidepressant activity in vivo. As environmental events and other risk factors contribute to depression through converging molecular and cellular mechanisms that disrupt neuronal function and morphology—resulting in dysfunction of the circuitry that is essential for mood regulation and cognitive function—we investigated the neurotrophic properties of Silexan in neuronal cell lines and primary hippocampal neurons. Results The antidepressant activity of Silexan (30 mg/kg BW) in the FST was comparable to the tricyclic antidepressant imipramine (20 mg/kg BW) after 9-day treatment. Silexan triggered neurite outgrowth and synaptogenesis in 2 different neuronal cell models and led to a significant increase in synaptogenesis in primary hippocampal neurons. Silexan led to a significant phosphorylation of protein kinase A and subsequent CREB phosphorylation. Conclusion Taken together, Silexan demonstrates antidepressant-like effects in cellular as well as animal models for antidepressant activity. Therefore, our data provides preclinical evidence for the clinical antidepressant effects of Silexan in patients with mixed depression and anxiety.
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29

Pochwat, Bartłomiej, Helena Domin, Anna Rafało-Ulińska, Bernadeta Szewczyk, and Gabriel Nowak. "Ketamine and Ro 25-6981 Reverse Behavioral Abnormalities in Rats Subjected to Dietary Zinc Restriction." International Journal of Molecular Sciences 21, no. 13 (July 6, 2020): 4791. http://dx.doi.org/10.3390/ijms21134791.

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Clinical and preclinical studies indicate that zinc (Zn) is an essential factor in the development and treatment of major depressive disorder (MDD). Conventional monoamine-based antidepressants mobilize zinc in the blood and brain of depressed patients as well as rodents. N-methyl-D-aspartate acid receptor (NMDAR) antagonists exhibit antidepressant-like activity. However, not much is known about the antidepressant efficacy of NMDAR antagonists in zinc-deficient (ZnD) animals. We evaluated the antidepressant-like activity of two NMDAR antagonists (ketamine; global NMDAR antagonist and Ro 25-6981 (Ro); selective antagonist of the GluN2B NMDAR subunit) in ZnD rats using the forced swim test (FST) and sucrose intake test (SIT). A single dose of either Ro 25-6981 or ketamine normalized depressive-like behaviors in ZnD rats; however, Ro was effective in both tests, while ketamine was only effective in the FST. Additionally, we investigated the mechanism of antidepressant action of Ro at the molecular (analysis of protein expression by Western blotting) and anatomical (density of dendritic spines by Golgi Cox-staining) levels. ZnD rats exhibited decreased phosphorylation of the p70S6K protein, and enhanced density of dendritic spines in the prefrontal cortex (PFC) compared to control rats. The antidepressant-like activity of Ro was associated with the increased phosphorylation of p70S6K and ERK in the PFC. In summary, single doses of the NMDAR antagonists ketamine and Ro exhibited antidepressant-like activity in the ZnD animal model of depression. Animals were only deprived of Zn for 4 weeks and the biochemical effects of Zn deprivation and Ro were investigated in the PFC and hippocampus. The shorter duration of dietary Zn restriction may be a limitation of the study. However, future studies with longer durations of dietary Zn restriction, as well as the investigation of multiple brain structures, are encouraged as a supplement to this study.
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Almeida, Lorena de Souza, Ianca Gontijo Cavalcante Santana, Lorrane Kelle da Silva Moreira, Larissa Córdova Turones, Germán Sanz, Boniek G. Vaz, Flávio S. de Carvalho, et al. "Neuropharmacological Activity of the New Piperazine Derivative 2-(4-((1- Phenyl-1H-Pyrazol-4-yl)Methyl)Piperazin-1-yl)Ethyl Acetate is Modulated by Serotonergic and GABAergic Pathways." CNS & Neurological Disorders - Drug Targets 21, no. 6 (July 2022): 520–32. http://dx.doi.org/10.2174/1871527320666211112173233.

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Background: Pharmacological treatments for mental disorders, such as anxiety and depression, present several limitations and adverse effects. Therefore, new pharmacotherapy with anxiolytic and antidepressant potential is necessary, and the study of compounds capable of interacting with more than one pharmacological target may provide new therapeutic options. Objectives: In this study, we proposed the design, synthesis of a new compound, 2-(4-((1- phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethyl acetate (LQFM192), pharmacological evaluation of its anxiolytic-like and antidepressant-like activities, as well as the possible mechanisms of action involved. Methods: Administration of LQFM192 was carried out prior to the exposure of male Swiss mice to behavioral tests, such as the elevated plus-maze and forced swimming test. The involvement of the serotonergic system was studied by pretreatment with WAY-100635 or p-chlorophenylalanine (PCPA) and the involvement of the benzodiazepine site of the GABAA receptor by pretreatment with flumazenil. Results: The treatment with LQFM192 at doses of 54 and 162 μmol/kg demonstrated anxiolyticlike activity that was blocked by WAY-100635, PCPA, and flumazenil pretreatments. The potential antidepressant-like activity was visualized at the same doses and blocked by WAY-100635 and PCPA. Conclusion: In summary, the anxiolytic-like activity of LQFM192 is mediated by the serotonergic system and the benzodiazepine site of the GABAA receptor, and the antidepressant-like activity through the serotonergic system.
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Zhao, Le, Zixu Zhang, Mingmei Zhou, Xiaojun Gou, Yang Zeng, Jing Song, Weini Ma, and Ying Xu. "A urinary metabolomics (GC-MS) strategy to evaluate the antidepressant-like effect of chlorogenic acid in adrenocorticotropic hormone-treated rats." RSC Advances 8, no. 17 (2018): 9141–51. http://dx.doi.org/10.1039/c8ra00074c.

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Chlorogenic acid showed antidepressant-like activity in chronic ACTH-treated rats, providing a potential drug candidate for prevention and treatment of tricyclic antidepressant treatment-resistant depression. Related metabolic pathways were shown.
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32

Sałaciak, Kinga, Monika Głuch-Lutwin, Agata Siwek, Małgorzata Szafarz, Grzegorz Kazek, Marek Bednarski, Leszek Nowiński, et al. "The antidepressant-like activity of chiral xanthone derivatives may be mediated by 5-HT1A receptor and β-arrestin signalling." Journal of Psychopharmacology 34, no. 12 (October 24, 2020): 1431–42. http://dx.doi.org/10.1177/0269881120959605.

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Background: Our previous studies showed that xanthone derivatives with N-(2-methoxyphenyl)piperazine fragment have an affinity to the 5-HT1A receptor and show antidepressant-like properties in rodents. In this study, we tested three xanthone derivatives, HBK-1 (R, S) and its enantiomers, in which we increased the distance between the piperazine and xanthone fragments by using a hydroxypropoxy linker. We hypothesized that this would increase the binding to the 5-HT1A receptor and consequently, pharmacological activity. Aims: We aimed to assess the in vitro and in vivo pharmacological activity of the xanthone derivatives. Methods: We evaluated the in vitro affinity for serotonin 5-HT1A and 5-HT2A receptors and serotonin transporter. We also determined the intrinsic activity at the 5-HT1A receptor. We investigated the antidepressant-like properties and safety after acute administration (dose range: 1.25–20 mg/kg) using the forced swim, tail suspension, locomotor activity, rotarod and chimney tests in mice. We also evaluated the basic pharmacokinetic parameters. Results: Our results indicated that the compounds showed a high affinity for the 5-HT1A receptor but very weak antagonistic properties in the Ca2+ mobilization assay; however, they showed significant agonistic properties in the β-arrestin recruitment assay. In both behavioural tests the studied xanthone derivatives showed antidepressant-like activity. Pre-treatment with p-chlorophenylalanine or WAY-100635 abolished their antidepressant-like activity. None of the compounds caused motor impairments at antidepressant-like doses. The racemate penetrated the blood–brain barrier and had a relatively high bioavailability after intraperitoneal administration. Conclusions: Xanthone derivatives with N-(2-methoxyphenyl)piperazine fragment and hydroxypropoxy linker show increased binding to the 5-HT1A receptor and may represent an attractive putative treatment candidate for depression.
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Lee, Mi-Sook, Young Han Kim, Bo-ram Lee, Seung-Hae Kwon, Won-Jin Moon, Kwan-Su Hong, Yun Seon Song, et al. "Novel Antidepressant-Like Activity of Caffeic Acid Phenethyl Ester Is Mediated by Enhanced Glucocorticoid Receptor Function in the Hippocampus." Evidence-Based Complementary and Alternative Medicine 2014 (2014): 1–10. http://dx.doi.org/10.1155/2014/646039.

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Caffeic acid phenethyl ester (CAPE) is an active component of propolis that has a variety of potential pharmacological effects. Although we previously demonstrated that propolis has antidepressant-like activity, the effect of CAPE on this activity remains unknown. The present study assessed whether treatment with CAPE (5, 10, and 20 µmol/kg for 21 days) has an antidepressant-like effect in mice subjected to chronic unpredictable stress via tail suspension (TST) and forced swim (FST) tests. CAPE administration induced behaviors consistent with an antidepressant effect, evidenced by decreased immobility in the TST and FST independent of any effect on serum corticosterone secretion. Western blots, conducted subsequent to behavioral assessment, revealed that CAPE significantly decreased glucocorticoid receptor phosphorylation at S234 (pGR(S234)), resulting in an increased pGR(S220/S234) ratio. We also observed negative correlations between pGR(S220)/(S234) and p38 mitogen-activated protein kinase (p38MAPK) phosphorylation, which was decreased by CAPE treatment. These findings suggest that CAPE treatment exerts an antidepressant-like effect via downregulation of p38MAPK phosphorylation, thereby contributing to enhanced GR function.
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Bambico, Francis Rodriguez, Zhuoliang Li, Meaghan Creed, Danilo De Gregorio, Mustansir Diwan, Jessica Li, Sean McNeill, Gabriella Gobbi, Roger Raymond, and José N. Nobrega. "A Key Role for Prefrontocortical Small Conductance Calcium-Activated Potassium Channels in Stress Adaptation and Rapid Antidepressant Response." Cerebral Cortex 30, no. 3 (September 3, 2019): 1559–72. http://dx.doi.org/10.1093/cercor/bhz187.

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Abstract The muscarinic acetylcholine receptor antagonist scopolamine elicits rapid antidepressant activity, but its underlying mechanism is not fully understood. In a chronic stress model, a single low-dose administration of scopolamine reversed depressive-like reactivity. This antidepressant-like effect was mediated via a muscarinic M1 receptor–SKC pathway because it was mimicked by intra-medial prefrontal cortex (intra-mPFC) infusions of scopolamine, of the M1 antagonist pirenzepine or of the SKC antagonist apamin, but not by the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine. Extracellular and whole-cell recordings revealed that scopolamine and ketamine attenuate the SKC-mediated action potential hyperpolarization current and rapidly enhance mPFC neuronal excitability within the therapeutically relevant time window. The SKC agonist 1-EBIO abrogated scopolamine-induced antidepressant activity at a dose that completely suppressed burst firing activity. Scopolamine also induced a slow-onset activation of raphe serotonergic neurons, which in turn was dependent on mPFC-induced neuroplasticity or excitatory input, since mPFC transection abolished this effect. These early behavioral and mPFC activational effects of scopolamine did not appear to depend on prefrontocortical brain-derived neurotrophic factor and serotonin-1A activity, classically linked to SSRIs, and suggest a novel mechanism associated with antidepressant response onset through SKC-mediated regulation of activity-dependent plasticity.
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Pilc, Andrzej, Agnieszka Pałucha-Poniewiera, Piotr Brański, Katarzyna Stachowicz, Anna Sławińska, Lucyna Pomierny-Chamioło, and Gabriel Nowak. "On the mechanism of antidepressant-like activity of mGlu5 allosteric modulators." Pharmacological Reports 65 (May 2013): 22–23. http://dx.doi.org/10.1016/s1734-1140(13)71290-8.

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Kedzierska, Ewa, and Izabela Wach. "Using tests and models to assess antidepressant-like activity in rodents." Current Issues in Pharmacy and Medical Sciences 29, no. 2 (June 1, 2016): 61–65. http://dx.doi.org/10.1515/cipms-2016-0013.

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Abstract In today's world, depression is one of the more prevalent forms of mental illness. According to WHO, about 10%-30% of all women and 7%-15% of all men are afflicted by depression at least once in their life-times. Today, depression is assessed to be affecting 350 million people. Regarding this issue, an important challenge for current psychopharmacology is to develop new, more effective pharmacotherapy and to understand the mechanism of action of known antidepressants. Furthermore, there is the necessity to improve the effectiveness of anti-depression treatment by way of bringing about an understanding of the neurobiology of this illness. In achieving these objectives, animal models of depression can be useful. Yet, presently, all available animal models of depression rely on two principles: the actions of known antidepressants or the responses to stress. In this paper, we present an overview of the most widely used animal tests and models that are employed in assessing antidepressant-like activity in rodents. These include amphetamine potentiation, reversal of reserpine action, the forced swimming test, the tail suspension test, learned helplessness, chronic mild stress and social defeat stress. Moreover, the advantages and major drawbacks of each model are also discussed.
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Papp, Mariusz, and Joanna Wieronska. "Antidepressant-like activity of amisulpride in two animal models of depression." Journal of Psychopharmacology 14, no. 1 (January 2000): 46–52. http://dx.doi.org/10.1177/026988110001400106.

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Inan, Salim Yalcin, Burak Cem Soner, and Ayse Saide Sahin. "Infralimbic cortex Rho-kinase inhibition causes antidepressant-like activity in rats." Progress in Neuro-Psychopharmacology and Biological Psychiatry 57 (March 2015): 36–43. http://dx.doi.org/10.1016/j.pnpbp.2014.10.008.

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39

Ccana-Ccapatinta, Gari V., Eveline D. Stolz, Paola F. da Costa, Stela M. K. Rates, and Gilsane L. von Poser. "Acylphloroglucinol Derivatives from Hypericum andinum: Antidepressant-like Activity of Andinin A." Journal of Natural Products 77, no. 10 (September 29, 2014): 2321–25. http://dx.doi.org/10.1021/np500426m.

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Gigliucci, Valentina, Grainne O’Dowd, Sheena Casey, Danielle Egan, Sinead Gibney, and Andrew Harkin. "Ketamine elicits sustained antidepressant-like activity via a serotonin-dependent mechanism." Psychopharmacology 228, no. 1 (March 2, 2013): 157–66. http://dx.doi.org/10.1007/s00213-013-3024-x.

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de Oliveira, Kely Navakoski, Philipe Costa, José Roberto Santin, Leonor Mazzambani, Cristiani Bürger, Cristiano Mora, Ricardo José Nunes, and Márcia Maria de Souza. "Synthesis and antidepressant-like activity evaluation of sulphonamides and sulphonyl-hydrazones." Bioorganic & Medicinal Chemistry 19, no. 14 (July 2011): 4295–306. http://dx.doi.org/10.1016/j.bmc.2011.05.056.

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Zhou, Ben Hong, Xiao Jun Li, Min Liu, Zhenhua Wu, and Xian Ming Hu. "Antidepressant-like activity of the Gastrodia elata ethanol extract in mice." Fitoterapia 77, no. 7-8 (December 2006): 592–94. http://dx.doi.org/10.1016/j.fitote.2006.06.016.

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43

Yoo, H. S., R. L. Tackett, J. B. Crabbe, B. N. Bunnell, and R. K. Dishman. "Antidepressant-like effects of physical activity versus imipramine: Neonatal clomipramine model." Psychobiology 28, no. 4 (December 2000): 540–49. http://dx.doi.org/10.3758/bf03332013.

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Zhang, Jing-Jing, Ting-Ting Gao, Yuan Wang, Jin-Liang Wang, Wei Guan, Ying-Jie Wang, Cheng-Niu Wang, Jian-Feng Liu, and Bo Jiang. "Andrographolide Exerts Significant Antidepressant-Like Effects Involving the Hippocampal BDNF System in Mice." International Journal of Neuropsychopharmacology 22, no. 9 (June 10, 2019): 585–600. http://dx.doi.org/10.1093/ijnp/pyz032.

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Abstract Background Major depressive disorder is a worldwide neuropsychiatric disorder associated with various symptoms, but current antidepressants used in clinical practice have various side effects and high failure rates. Andrographolide is the main bioactive ingredient of Andrographis paniculata and exhibits numerous pharmacological actions. This study aimed to evaluate the antidepressant-like effects of andrographolide in male C57BL/6J mice. Methods The antidepressant-like effects of andrographolide in mice were explored in a forced swim test, tail suspension test, and chronic unpredictable mild stress model of depression. Western blotting and immunofluorescence were further performed to assess the effects of chronic unpredictable mild stress and andrographolide on the brain-derived neurotrophic factor signalling cascade and hippocampal neurogenesis. Moreover, a pharmacological inhibitor (K252a) and a lentiviral-short hairpin RNA (LV-TrkB-shRNA) were used to clarify the antidepressant-like mechanism of andrographolide. Results Andrographolide exhibited antidepressant-like potential in the forced swim test and tail suspension test without influencing the locomotor activity of mice. Repeated andrographolide treatment not only produced significant antidepressant-like effects in the chronic unpredictable mild stress model but also prevented the decreasing effects of chronic unpredictable mild stress on hippocampal brain-derived neurotrophic factor signalling and neurogenesis in mice. Importantly, blockade of the hippocampal brain-derived neurotrophic factor system by K252a and TrkB-shRNA fully abolished the antidepressant-like effects of andrographolide in mice. Conclusions Andrographolide exerts antidepressant-like effects in mice via promoting the hippocampal brain-derived neurotrophic factor signalling cascade.
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45

Ito, N., T. Nagai, T. Oikawa, H. Yamada, and T. Hanawa. "Antidepressant-like Effect ofl-perillaldehyde in Stress-induced Depression-like Model Mice through Regulation of the Olfactory Nervous System." Evidence-Based Complementary and Alternative Medicine 2011 (2011): 1–5. http://dx.doi.org/10.1093/ecam/nen045.

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Perillae Herba (a leaf ofPerilla frutescens) has been prescribed as one of the component herbs in certain Kampo (Japanese herbal) medicines that are used clinically for the improvement of depressive mood.l-Perillaldehyde (PAH) is a major component in the essential oil containing in Perillae Herba, but its antidepressant-like effect has not been reported. To clarify the antidepressant-like effect of PAH, the inhaled effect of PAH on stress-induced depression-like model mice prepared by subjection to a combination of forced swimming and chronic mild stresses was investigated. The degree of the depression-like state was measured by the animal's duration of immobility using a forced swimming test. Inhalation of PAH (0.0965 and 0.965 mg/mouse/day, 9 days) significantly shortened the duration of immobility of the depression-like model mice and did not affect locomotor activity. However, another odor substance, cinnamaldehyde containing in Cinnamomi Cortex, exhibited no reduction in the immobility. The reduction in the immobility induced by the inhalation of PAH was prevented on anosmia-induced mice prepared by intranasal irrigation with zinc sulfate. These results suggest that the inhalation of PAH shows antidepressant-like activity through the olfactory nervous function.
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46

Kolla, Rohan, and Suneel I. Majagi. "Effect of vitamin D on depression: an experimental study." International Journal of Basic & Clinical Pharmacology 8, no. 9 (August 28, 2019): 2033. http://dx.doi.org/10.18203/2319-2003.ijbcp20194112.

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Background: There is a scarcity of studies regarding antidepressant activity of vitamin D in animals while there are some contradictory reports regarding the same in humans. Therefore the present study was planned to investigate the antidepressant effect of vitamin D and its interaction with standard antidepressant drugs in animals.Methods: Forced swim test (FST) in adult male Wistar rats and tail suspension test (TST) in adult male Swiss albino mice were used to investigate antidepressant activity of vitamin D administered in single dose and multiple doses. Imipramine, a tri-cyclic antidepressant and fluoxetine, a selective serotonin reuptake inhibitor were used as standard antidepressant drugs. For interaction studies, half the therapeutic equivalent dose of vitamin D was combined with sub-effective dose (SED) of imipramine or fluoxetine. Data was expressed as Mean±SD and analyzed by standard statistical tests. P<0.05= significant. Present study was ethically approved.Results: Single dose administration of vitamin D did not show significant antidepressant effect either in FST or TST. Multiple dose administration of vitamin D showed significant antidepressant activity in TST but not in FST. Combination of vitamin D (half dose) with SED of either standard antidepressant drugs did not show any significant antidepressant activity. None of the treatment groups showed any significant difference on locomotor activity.Conclusions: In the present study, multiple dose administration of vitamin D showed some antidepressant activity. Further studies are needed to confirm and elaborate the role of vitamin D in behavioral disorders like depression.
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Huang, Zhen, Qing-Qiu Mao, Xiao-Ming Zhong, Zhao-Yi Li, Feng-Mei Qiu, and Siu-Po Ip. "Mechanistic Study on the Antidepressant-Like Effect of Danggui-Shaoyao-San, a Chinese Herbal Formula." Evidence-Based Complementary and Alternative Medicine 2012 (2012): 1–7. http://dx.doi.org/10.1155/2012/173565.

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Danggui-Shaoyao-San (DSS), a famous Chinese herbal formula, has been widely used in the treatment of various diseases. Previous studies have shown that DSS produces antidepressant-like effect in rodents. This study aims to investigate the mechanism(s) underlying the antidepressant-like action of DDS. The results showed that DSS treatment significantly antagonized reserpine-induced ptosis in mice. In addition, DSS treatment significantly increased sucrose consumption in chronic unpredictable stress- (CUS-) treated mice. DSS treatment also markedly attenuated CUS-induced decreases in noradrenaline and dopamine concentrations in mouse brain. Furthermore, DSS treatment significantly reversed CUS-induced increase in serum malondialdehyde (MDA) content and decrease in serum superoxide dismutase (SOD) activity in mice. The results suggest that the antidepressant-like activity of DSS is probably mediated by the modulation of central monoamine neurotransmitter systems and the reduction of oxidative stress.
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Turan, Nazlı, Ümide Demir Özkay, Nafiz Öncü Can, and Özgür Devrim Can. "Investigating the Antidepressant-like Effects of some Benzimidazolepiperidine Derivatives by In-Vivo Experimental Methods." Letters in Drug Design & Discovery 16, no. 3 (January 15, 2019): 341–46. http://dx.doi.org/10.2174/1570180815666181004103112.

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Background: Benzimidazole and piperidine rings are important pharmacophore groups for drug design studies. </P><P> Objective: In this study, we aimed to investigate the antidepressant-like activity of some 2-(4- substituted-phenyl)-1-[2-(piperidin-1-yl)ethyl]-1H-benzimidazole derivatives. </P><P> Methods: Tail-suspension Test (TST) and Modified Forced Swimming Tests (MFST) were used to assess antidepressant-like activities of the test compounds. Moreover, locomotor activity performances of the animals were evaluated by an activity cage device. </P><P> Results: In the TST and MFST, compounds 2c-2h (10 mg/kg) and the reference drug fluoxetine (20 mg/kg) significantly reduced the immobility time of mice indicating the antidepressant-like activities of these compounds. Further, in MFST, the same compounds induced significant enhancement in the duration of active swimming behaviors without affecting the climbing performance of the animals. This prolongation in the swimming time, similar to fluoxetine, pointed out that antidepressant- like activity of the compounds 2c-2h might be related to the serotonergic rather than noradrenergic mechanisms. Besides, results of the activity cage tests demonstrated that none of the tested compounds caused an alteration in the locomotor activities of mice, signifying that antidepressantlike effects presented in this study were specific. </P><P> Conclusion: In conclusion, results of this present study supported the previous papers reporting the therapeutic potential of compounds carrying benzimidazole and/or piperidine rings in their structure and emphasized, once again, the importance of these pharmacophore groups in drug design studies.
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Szopa, Aleksandra, Ewa Poleszak, Elżbieta Wyska, Anna Serefko, Sylwia Wośko, Aleksandra Wlaź, Mateusz Pieróg, Andrzej Wróbel, and Piotr Wlaź. "Caffeine enhances the antidepressant-like activity of common antidepressant drugs in the forced swim test in mice." Naunyn-Schmiedeberg's Archives of Pharmacology 389, no. 2 (November 27, 2015): 211–21. http://dx.doi.org/10.1007/s00210-015-1189-z.

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Nguyen, Thanh Trung, Yuki Kambe, and Atsuro Miyata. "Chronic Royal Jelly Administration Induced Antidepressant-Like Effects Through Increased Sirtuin1 and Oxidative Phosphorylation Protein Expression in the Amygdala of Mice." Current Molecular Pharmacology 14, no. 2 (December 31, 2020): 115–22. http://dx.doi.org/10.2174/1874467213666200424160153.

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Background: Major depressive disorder (MDD) is a common psychological disorder worldwide. However, one-third of patients with MDD are resistant to the present antidepressant medicine which regulates monoamine contents in the brain. Thus, another drug target is strongly required. Much evidence strongly suggests that sirtuin1, which is the key factor to regulate mitochondrial activity, may be implicated in MDD. Objective: Since it is suggested that royal jelly (RJ) ameliorated depressive-like behavior and affected mitochondrial activity in mice, we hypothesized RJ could be an alternative medicine against MDD which acts via sirtuin1 signaling to improve mitochondrial activity. Methods: In the present study, we applied a mouse model of MDD to investigate the effect of RJ on the depressive-like behavior and the sirtuin1 signaling on mitochondrial activity. Results: Our results indicated that either the oral administration of RJ for 12 days or single intracerebroventricular (i.c.v.) injection decreased the duration of immobility in the tail suspension test, which suggested that RJ had an antidepressant-like effect. Moreover, sirtuin1 protein expression increased in mice following RJ treatment in the amygdala region, but not in the other brain regions. Similarly, the expressions of oxidative phosphorylation (OXPHOS) related proteins increased in the amygdala regions, but not in the hippocampal regions. Conclusion: The increase of sirtuin1 and OXPHOS protein expression may at least in part contribute to the antidepressant-like effect of the RJ pathway, and RJ may have the potential to be a novel antidepressant drug.
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