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.

Cognitive impairment in major depression and the mGlu2 receptor as a therapeutic target

“…Furthermore, such models appear valuable to study the persistence of cognitive deficits, and their sensitivity to classical antidepressant treatment. Indeed, certain cognitive deficits such as object recognition seem to be ameliorated (Orsetti et al, 2007;Elizalde et al, 2008), whereas others, such as working memory or spatial learning deficits, remain generally insensitive to classical antidepressant treatment (Bessa et al, 2009b;Andreasen et al, 2011). Altogether, this set of data suggests that a potential dissociation between mood-dependent and independent cognitive impairments, as described in patients with MDD, can be recapitulated in the CMS model.…”

“…Interestingly, these models also recapitulate the deficits in cognitive domains observed in MDD. Indeed, these models induce impairments in working memory evaluated in spontaneous or delayed alternation tasks (Mizoguchi et al, 2000;Song et al, 2006;Henningsen et al, 2009;Palumbo et al, 2010;Andreasen et al, 2011;Yu et al, 2011), cognitive flexibility assessed in attentional set shifting (Lapiz et al, 2007;Bondi et al, 2008Bondi et al, , 2010, spatial reversal learning without affecting acquisition (Cerqueira et al, 2005;Hill et al, 2005;Bessa et al, 2009b;Bisaz et al, 2011) and fear extinction (Garcia et al, 2008;Gourley et al, 2009), without affecting fear learning processes (or facilitating them e see Sandi et al, 2001;Henningsen et al, 2009;Yu et al, 2011). Learning and memory deficits in spatial learning and object recognition also develop (Orsetti et al, 2007;Elizalde et al, 2008;Li et al, 2008).…”

Impact of Tobacco Regulation on Animal Research: New Perspectives and Opportunities

“…This model has been cited as having high translational validity to depressive disorders (Pryce et al, 2011). Evidence suggests that nicotine may have antidepressant effects in the learned helplessness model of depression (Semba, Mataki, Yamada, Nankai, & Toru, 1998), as well as in other animal models of depression (Picciotto, Brunzell, & Caldarone, 2002;Andreasen, Henningsen, Bate, Christiansen, & Wiborg, 2011); however, these studies have generally used subcutaneous nicotine, often acute noncontingent, which limits their relevance to cigarette smoking and cessation in the depressed individual. Combined use of animal models of depression and self-administration can examine issues such as the initial response to nicotine, the nicotine threshold in rats displaying depression-like symptoms, the impact of nicotine self-administration on the signs of depression, the impact of nicotine history on threshold in these rats compared with controls, the emergence or worsening or depressive and/or withdrawal symptoms after nicotine reduction, and interactions between antidepressants and different doses of nicotine.…”

Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy

“…Clinical data also suggest their involvement in the pathogenesis of several disorders, including Alzheimer's disease, Parkinson's disease, schizophrenia, and depression. On the basis of a variety of preclinical and (to a lesser extent) clinical models, it has been hypothesized that nAChRs may be a therapeutic target for studying the effects of L-form nicotine (63). In 2001, the crystal structure of the nAChR protein allowed its characterization as an ACh-binding protein (64).…”