Antidepressant Effect In Forced Swimming Test Research Articles

Reversal effect of Riparin IV in depression and anxiety caused by corticosterone chronic administration in mice

Mental disorders have a multifactorial etiology and stress presents as one of the causal factors. In depression, it is suggested that high cortisol concentration contributes directly to the pathology of this disease. Based on that, the study aims to evaluate the potential antidepressant effect of Riparin IV (Rip IV) in mice submitted to chronic stress model by repeated corticosterone administration. Female Swiss mice were selected into four groups: control (Ctrl), corticosterone (Cort), Riparin IV (Cort + Rip IV) and fluvoxamine (Cort + Flu). Three groups were administrated subcutaneously (SC) with corticosterone (20 mg/kg) during twenty-one days, while the control group received only vehicle. After the fourteenth day, groups were administrated tested drugs: Riparin IV, fluvoxamine or distilled water, by gavage, 1 h after subcutaneous injections. After the final treatment, animals were exposed to behavioral models such as forced swimming test (FST), tail suspension test (TST), open field test (OFT), elevated plus maze (EPM) and sucrose preference test (SPT). The hippocampus was also removed for the determination of BDNF levels. Corticosterone treatment altered all parameters in behavioral tests, leading to a depressive- and anxious-like behavior. Riparin IV and fluvoxamine exhibit antidepressant effect in FST, TST and SPT. In EPM and OFT, treatment displayed anxiolytic effect without alteration of locomotor activity. Corticosterone administration decreased BDNF levels and Riparin IV could reestablish them, indicating that its antidepressant effect may be related to ability to ameliorate hippocampal neurogenesis. These findings suggest that Riparin IV improves the depressive and anxious symptoms after chronic stress and could be a new alternative treatment for patients with depression.

Resistance to depression through interference of opioid and nitrergic systems in bile-duct ligated mice

This study was done to investigate the effects of opioid and nitrergic systems on depression in an experimental model of cholestasis in mice, since elevated levels of these substances are seen in cholestatic subjects. Bile duct ligated (BDL) and sham-operated mice were forced to swim individually and the immobility time in the last 4min of the 6min test was evaluated to determine the effects of cholestasis on depression. To assess the possible involvement of endogenous opioids and nitric oxide (NO), effective and sub-effective doses of naltrexone an antagonist of opioid receptors, and N-nitro-l-arginine methyl ester (L-NAME) a non-specific NO synthase inhibitor, were administrated acutely and chronically to BDL and Sham-operated mice and then their immobility time was measured in forced swimming test (FST). The immobility time significantly decreased after bile-duct ligation. Naltrexone and L-NAME significantly reversed antidepressant like effect of cholestasis. Co-administration of sub-effective doses of naltrexone and L-NAME also reversed antidepressant effect in FST in chronic administration. But acute drug administration did not reverse the anti-depressant effect of cholestasis. We have shown that elevated levels of endogenous opioids and NO in cholestatic mice induce an anti depressant like effect, causing a reduction in the mice immobility time in FST. And the study also showed the predominant effect of opioid system and NO modulation of that in anti-depressant like effect of cholestasis.

Neuropharmacological in vivo effects and phytochemical profile of the extract from the aerial parts of Heteropterys brachiata (L.) DC. (Malpighiaceae)

Ethnopharmacological relevanceHeteropterys brachiata is a plant species that has been used in traditional Mexican medicine for the treatment of nervous disorders. Aim of the studyTo evaluate the anxiolytic, anticonvulsant, antidepressant and sedative effects produced by the methanolic extract of Heteropterys brachiata (HbMeOH) in ICR mice. Additionally, we determine the acute toxicity profiles of the extract and the presence of its main constituents. Material and methodsThe neuropharmacological effects of the extract were evaluated using a variety of models, such as the elevated plus maze (EPM), the forced swimming test (FST), the pentobarbital potentiation test (PTBt), pentylenetetrazole-induced seizures test (PTZt), and the open field test (OFT). HPLC was employed for obtention of phytochemical profile. ResultsHbMeOH produced a significant antidepressant effect in FST at 500 and 750mg/kg doses, while doses from 500 to 1500mg/kg exhibited a clear dose-dependent anxiolytic activity in EPM. A dose of 500mg/kg showed a significant anticonvulsant activity in PTZt and an absence of sedation effects in PTBt. The main compounds of HbMeOH were chlorogenic acid and chlorogenic acid methyl ester, as well as less abundant terpene-type compounds. Furthermore, the extract was either safe with no deaths in mice treated orally with 2000mg/kg. ConclusionsHbMeOH extract which contains mainly hydroxycinnamic acids and triterpene-type compounds, possesses antidepressant, anxiolytic and anticonvulsive properties and can be considered safe or of low toxicity when orally administrated. These findings lend pharmacological justification to the traditional use of Heteropterys brachiata in the treatment of nervous disorders.

P13 Resistance to depression through interference of opioid and nitrergic systems in bile-duct ligated (BDL) mice

<h3>Objective</h3> Endogenous opioids and nitric oxide (NO) are signalling molecules that play important roles in depressive disorders. Elevated levels of these substances are seen in cholestasis subjects. This study was undertaken to investigate the effect of opioid and nitrergic systems on depression in an experimental model of cholestasis. <h3>Method</h3> Bile duct ligated (BDL) and sham-operated mice were forced to swim individually and the immobility time of the last 4 min was evaluated to determine the effect of cholestasis on depression. To assess the possible involvement of endogenous opioids and NO, an antagonist of opioids receptors, naltrexone (20 mg/kg, i.p.), and a non-specific NOS inhibitor, N-nitro-l-arginine methyl ester (L-NAME, 20 mg/kg, i.p.), and sub-effective doses of both of them (3 mg/kg, i.p.) were administrated acutely, one hour before forced swimming test (FST). And chronically, both for 5 and 7 days after operation, to BDL and Sham-operated mice and then were tested by FST. <h3>Results</h3> The immobility time significantly decreased after bile duct ligation. naltrexone and L-NAME significantly reversed antidepressant like effect of cholestasis in both 5 and 7 days groups .Co-administration of sub-effective doses of naltrexone and L-NAME also reversed antidepressant effect in FST in chronic administration, and significant difference was observed in immobility times between all 5 and 7 days groups. But acute drug administration did not reverse the anti-depressant effect of cholestasis. <h3>Conclusion</h3> We have shown for the first time that elevated levels of endogenous opioids and nitric oxide (NO) due to bile-duct ligation in mice induce an antidepressant like effect, causing a reduction in mice immobility time in FST. The effect was reversed with blockage of nitrergic and opioid systems. And also study showed the predominant effect of opioid system and NO modulation of that in anti-depressant like effect of cholestasis.

Effects of a putative antidepressant with a rapid onset of action in defeated mice with different coping strategies

There is evidence suggesting that stressful social events may result in depressive-like disorders, but the development of these disorders depend on the way in which people cope with stress. Although antidepressants are useful their drawback is a delay in the therapeutic effects, moreover not all the patients show an adequate response to this treatment. The aim of this study was to analyse the effect of RS 67333, which is a 5-HT(4) receptor partial agonist and a putative antidepressant which exhibits a rapid onset of action and to determine whether this drug reverses the behavioural and physiological effects that are generated by chronic defeat in subjects who manifest a more vulnerable profile in their response to stress. Male mice were exposed to defeat for 21 consecutive days using a sensorial contact model. After 18 days of defeat, 2 groups of subjects were established, active and passive, in accordance with the behaviour that was manifested during social confrontation, and drug treatment was initiated for 5 days. Finally, the animals were subjected to a forced swimming test (FST). The results revealed higher corticosterone levels in passive mice after the last defeat. Additionally, 3 days after the last defeat, they showed lower corticosterone levels and higher splenic IL-6 and TNF-α levels and hypothalamic GR mRNA levels when compared to their active and manipulated control counterparts. Passive mice had higher 5-HT(1A) receptor mRNA levels than the manipulated controls and a lower MR/GR ratio than active mice. Similar to stress, the drug increased hypothalamic GR mRNA levels, but it did not affect other measured physiological variables or social behaviour, which suggested that the mechanism of this drug is not the most adequate for reversing stress-induced effects in this model. Nevertheless, the treatment increased swimming and decreased immobility in the FST, suggesting an antidepressant potential for this drug.