Nicotine reverses anhedonic-like response and cognitive impairment in the rat chronic mild stress model of depression: comparison with sertraline

Abstract

Smoking rates among depressed individuals are higher than is observed in the background population, and nicotine alleviates depressive symptoms. In rodents, nicotine shows antidepressant-like effects in the forced swim and learned helplessness paradigms. Clinical depression is associated with both anhedonia and cognitive impairments. In rats, chronic mild stress (CMS) decreases voluntary sucrose intake, reflecting an anhedonic-like state, and impairs performance in the spontaneous alternation behaviour (SAB) test, suggesting impaired cognitive function. Here, we examine the effect of chronic treatment of nicotine (0.4 mg/kg/day) and sertraline (5 mg/kg/day) on CMS-induced anhedonic-like behaviour and impairment in the SAB test. Nicotine and sertraline administered individually or in combination show significant and equally efficacious reversal of the CMS-induced decrease in sucrose intake, implying there is no additive or synergistic effect of the nicotine + sertraline combination. In the SAB test, nicotine, but not sertraline or nicotine + sertraline, reversed the CMS-induced impairment. The present results show that the effect of nicotine on a CMS-induced anhedonic-like state in rats is similar to that of a standard antidepressant drug. Moreover, the data suggest that nicotine alleviates CMS-induced cognitive disturbance. A treatment strategy involving the targeting of nicotinic acetylcholine receptors may prove beneficial for emotional and cognitive disturbances associated with depression.