Letteratura scientifica selezionata sul tema "Antidepressant-like activity"

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.

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.

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.

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.

Espécies do gênero Valeriana são tradicionalmente utilizadas no tratamento de insônia e ansiedade. Valepotriatos constituem um importante grupo de metabólitos do gênero que contribui para os efeitos farmacológicos. Trabalhos recentes demonstraram a atividade do tipo antidepressiva de diversas espécies de Valeriana, como V. glechomifolia, nativa do Rio Grande Sul, o que representa uma nova abordagem para o emprego terapêutico do gênero. Objetivos: Investigar o envolvimento da neurotransmissão monoaminérgica na atividade antidepressiva de um extrato de V. glechomifolia obtido por dióxido de carbono supercrítico (SCCO2) e avaliar a influência do tempo e condições de armazenamento no teor de valepotriatos diênicos. Materiais e Métodos: Partes aéreas e subterrâneas de V. glechomifolia foram submetidas a SCCO2 e o extrato obtido foi armazenado (a - 20ºC) seco ou solubilizado em metanol. As concentrações de valepotriatos diênicos foram determinadas, durante 8 meses, através de cromatografia líquida de alta eficiência. A atividade do tipo antidepressiva foi avaliada em camundongos no teste da suspensão pela cauda (TSC) e da natação forçada (TNF). Para a investigação do envolvimento do sistema monoaminérgico, antagonistas de receptores de monoaminas e um inibidor da síntese de serotonina foram administrados. A interação do extrato com antidepressivos convencionais foi avaliada no TNF através da co-administração de doses sub-efetivas. Resultados e Conclusões: V. glechomifolia reduziu a imobilidade dos animais no TSC e TNF, confirmando o potencial antidepressivo. O efeito foi mediado pelos sistemas neurotransmissores noradrenérgico (receptor α2) e dopaminérgico (receptores D1 e D2), o que representa uma ação dual diferenciada. V. glechomifolia potencializou o efeito de imipramina, desipramina e bupropiona no TNF. Em ambas as condições de armazenamento do extrato, observaram-se conversão molecular de valepotriatos diênicos em valtrato. Houve formação de produtos de degradação somente quando o extrato foi armazenado em metanol.
Species of the genus Valeriana are traditionally used to treat sleep disorders and anxiety. Valepotriates represent an important group of metabolites that contribute to the pharmacological properties of the genus. Studies have demonstrated the antidepressant-like activity of Valeriana species, like V. glechomifolia, a south Brazil native species, representing a new approach to the therapeutic use of the genus. Objectives: To further investigate the antidepressant-like activity of a V. glechomifolia supercritical carbon dioxide (SCCO2) extract as well as to evaluate the influence of time and storage conditions on diene valepotriates content of this extract. Material and Methods: Aerial and subterranean parts of V. glechomifolia were submitted to SCCO2 and the extract was stored (at -20 ºC) dry or in methanol. Diene valepotriates concentrations were determined through 8 months by high efficiency liquid chromatography. The antidepressant-like activity was evaluated in mice forced swimming test (FST) or tail suspension test (TST). To investigate the involvement of the monoaminergic system in this effect, different groups of mice were pre-treated with monoamine receptors antagonists or an inhibitor of serotonin synthesis. The interaction of the extract with antidepressants was evaluated in the FST by mice co-administration of sub-effective doses. Results and Conclusions: V. glechomifolia was active in the FST and TST, confirming its antidepressant-like effect, which was impaired by adrenergic (α2) and dopaminergic D1 and D2 antagonists, representing a distinct dual action. V. glechomifolia potentiated the antidepressant-like effect of imipramine, desipramine and bupropione in the FST. In both conditions of extract storage, a molecular interconvertion of diene valepotriates into valtrate was observed. Degradation products formation occurred only when the extract was stored in methanol.

Previously it was shown that neuropeptide cyclo-L-prolylglycine (CPG) is a positive modulator of AMPA receptors, which increases BDNF level in neuronal cell cultures. The spectrum of CPG’s pharmacological effects corresponds to that of BDNF. Dipeptide N-phenylacetyl-glycyl-L-proline ethyl ester (GZK-111) was designed and synthesized as a linear analog of CPG. The aim of the present work was to reveal the pharmacological profile of GZK-111. Dipeptide GZK-111 was shown to metabolize into CPG in vitro and increased cell survival by 28% at concentrations of 10-7–10-6 M in a Parkinson’s disease cell model. In a model of cerebral ischemia, GZK-111, at a dose of 0.5 mg/kg, i.p., was found to have neuroprotective effects, reducing the cerebral infarct volume by 1.6 times. Similar to CPG, GZK-111, at the range 0.1–1.0 mg/kg, i.p., possessed a stereospecific antiamnesic activity. A significant anxiolytic effect was observed at a dose of 1.5 mg/kg. GZK-111, at the range 0.5–4.0 mg/kg, i.p., demonstrated analgesic activity. GZK-111, at a dose of 10 mg/kg/7 days, i.p., possessed antidepressant-like activity. So, the neuroprotective, nootropic, antihypoxic, anxiolytic, antidepressant-like, and analgesic effects of GZK-111 were revealed. Thus, GZK-111 can be considered as a pharmacologically active pro-ampakine with a BDNF-ergic mechanism of action.

Ketamine is a phencyclidine derivative and N-methyl-D-aspartate receptor antagonist, widely popular as a dissociative anesthetic. Its use as an anesthetic in humans was progressively fallen out due to its associated adverse effects and the emergence of newer and safer anesthetics. In recent few decades, various reports related to its efficacy in the treatment of resistant depression with anti-suicidal potential draw significant attention from researchers around the globe. The rapid clinical effect of ketamine within hours as compared to traditional antidepressants that take several weeks makes it a hot topic in antidepressant research. Studies conducted in the recent past suggest its mechanism of action through glutamate modulation via receptors like NMDA, AMPA as well as downregulation of BDNF etc. This chapter will shed light on the various mechanisms of ketamine related to antidepressant activity. Along with that its pharmacokinetics, toxicology and ongoing clinical trials will also be discussed.