Effects of the novel antidepressant milnacipran in a chronic mild stress model of depression

Abstract

The chronic mild stress (CMS) model of depression may serve as a suitable research tool for studying the action of novel antidepressants (i.e., both efficacy and onset of action). The CMS-induced sub-sensitivity to reward is reversed by chronic treatment with antidepressant drugs. The effect of the serotonin and norepinephrine reuptake inhibitor (SNRI), milnacipran, was investigated on the CMS model in rats in comparison with imipramine. The CMS model of depression consisted in subjecting rats to several mild stressors for a prolonged period of time, which resulted in a decrease in their responsiveness to rewarding stimuli. This deficit was monitored by a decrease in the consumption of a 1% sucrose solution. Stressed and control animals received daily for 5 weeks injections of vehicle, imipramine (10 mg/ kg) or milnacipran (3, 10, and 30 mg/kg). CMS caused a decrease in the consumption of the 1% sucrose solution. The deficit in sucrose consumption in stressed animals was reversed by imipramine and milnacipran. The effect of milnacipran was gradual, dose-dependent, and was maintained for one week after stopping drug treatment. Neither imipramine nor milnacipran modified the behavior of control animals. Milnacipran is active in the CMS model of depression as expected from its clinically demonstrated antidepressant effect. Drug Dev.

Attenuation of chronic mild stress-induced ‘anhedonia’ by asenapine is not associated with a ‘hedonic’ profile in intracranial self-stimulation

“…Furthermore, in two independent cohorts, 0.6 mg/kg asenapine gradually restored sucrose consumption in CMS-exposed rats without affecting controls. The reversal of CMS-induced declines in sucrose consumption by imipramine observed in both treatment cohorts is consistent with many previous reports (Bekris et al, 2005;Jang et al, 2004;Papp and Wieronska, 2000;Papp et al, 1996Papp et al, , 2004. Importantly, the timing and magnitude of effects with asenapine were comparable to those of imipramine.…”

“…Sucrose testing during the period of exposure to stress was carried out once a week, with weekly sucrose testing always carried out during the stress-free period. This procedure reliably reduces daily sucrose intake in rats (Bekris et al, 2005;Jang et al, 2004;Papp and Wieronska, 2000;Papp et al, 1996Papp et al, , 2004.…”

“…In the second, the effects of asenapine were replicated and compared with vehicle treatment, along with olanzapine and risperidone. In both experiments, the antidepressant imipramine served as an active control that has previously been shown to reverse CMSinduced anhedonia (Papp et al, 1994a(Papp et al, , 1996(Papp et al, , 2004.…”

“…CMS-exposed rats develop a constellation of neurobehavioral and physiologic impairments, the most prominent of which is a substantially decreased responsiveness to positively reinforcing stimuli. This 'anhedonic' state has most frequently been characterized as a reduction in the consumption of a highly palatable sucrose solution (Bekris et al, 2005;Jang et al, 2004;Papp and Wieronska, 2000;Papp et al, 1996Papp et al, , 2004, but it has also been indexed using place preference (Muscat et al, 1992), maintenance coat condition (Mineur et al, 2006), plus maze, social avoidance and forced-swim tests (Griebel et al, 2002 a,b;Kompagne et al, 2008), sleep architecture (Cheeta et al, 1997) and intracranial self-stimulation (ICSS) paradigms (Nielsen et al, 2000;Papp et al, 1993). Further, unpredictable CMS has been shown to decrease the rate of neurogenesis in the hippocampus of mice, an observation of significant interest because many antidepressants have been shown to promote neurogenesis (Alonso et al, 2004;Mineur et al, 2007).…”

Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health

“…It has been observed that consuming breakfast leads to a number of affirmative influences on the cognitive activity of well-fed children [ 11 , 12 ]. The elevated hormone content and enzyme functions signal towards sensitivity of brain for stress [ 13 ]. The high stress circumstances may trigger depression and in adverse manner alter behavioral, learning, and biochemical activities.…”