Depressive characteristics of FSL rats: Involvement of central nicotinic receptors

Antidepressant effects of acute or chronic nicotine treatments in swim test immobility of Flinders sensitive line (FSL) rats, an animal model of depre ssion, were recently demonstrated (Tizabi et al. Psychopharmacology 142:193 , 1999). In the present study we sought to determine whether the antidepres sant effects of nicotine could be blocked by the nicotinic antagonist, meca mylamine (MEC). Moreover. the effects of chronic nicotine treatment on [H-3 ]cytisine binding in discrete brain regions of FSL and their control Flinde rs resistant line (FRL) rats were also evaluated. Adult male FSL rats were treated with MEC (0.5 mg/kg) 20 min prior to an acute or chronic nicotine a dministration. MEC by itself did not affect the immobility in swim test. Ho wever, it completely blocked the acute or chronic nicotine effects. Daily n icotine injection (0.4 mg/kg/day for 14 days) resulted in an increase in [H -3]cytisine binding primarily in the FRL rats. An increase in nicotinic rec eptor binding following chronic nicotine administration is believed to refl ect desensitization of these receptors. These findings, coupled with previo us observation of higher basal nicotinic receptors in FSL rats, further sup port the involvement of central nicotinic receptors in depressive character istics of these rats. Moreover, the data suggest therapeutic potential for selective nicotinic receptor agonists in depressive disorders. (C) 2000 Els evier Science Inc.