Antidepressant effects of nicotine in an animal model of depression

Epidemiological studies indicate a high incidence of cigarette smoking amon g depressed individuals. Moreover, individuals with a history of depression have a much harder time giving up smoking. It has been postulated that smo king may reflect an attempt at self-medication with nicotine by these indiv iduals. Although some animal and human studies suggest that nicotine may ac t as an antidepressant, further verification of this hypothesis and involve ment of nicotinic cholinergic system in depressive symptoms is required. Fl inders Sensitive Line (FSL) rats have been proposed as an animal model of d epression. These rats, selectively bred for their hyperresponsiveness to ch olinergic stimulation, show an exaggerated immobility in the forced swim te st compared to their control Flinders Resistant Line (FRL) rats. Acute or c hronic (14 days) administration of nicotine (0.4 mg/kg SC) significantly im proved the performance of the FSL but not the FRL rats in the swim test. Th e effects of nicotine on swim test were dissociable from its effects on loc omotor activity. Moreover, the FSL rats had significantly higher [H-3]cytis ine binding (selective for the alpha(4)beta(2) nicotinic receptor subtype) but not [I-125]alpha-bungarotoxin binding (selective for the alpha(7) subty pe) in the frontal cortex, striatum, midbrain and colliculi compared to FRL rats. These data strongly implicate the involvement of central nicotinic r eceptors in the depressive characteristics of the FSL rats, and suggest tha t nicotinic agonists may have therapeutic benefits in depressive disorders.