The effects of 5-HT3 receptor antagonists (ondansetron 0.1 mg kg-1 SC 30 min; bemesetron 0.03 mg kg-1 SC 45 min) on nicotine-induced increases in locomotor activity were measured in male Sprague-Dawley rats. Intermittent daily injections of nicotine (0.3-1.2 mg kg-1 SC 30 min) resulted in increased locomotor activity as measured by photocell counts. The effect of nicotine was not affected by administration of the 5-HT3 receptor antagonists at doses that are reported to block nicotine- and morphine-induced place-preference conditioning. Neither of the 5-HT3 receptor antagonists tested affected activity counts in vehicle treated animals. Nicotine-induced hyperactivity was blocked by the dopamine antagonist haloperidol (0.03 mg kg-1 SC 2 h) and by the nicotinic antagonist mecamylamine (1 mg kg-1 SC 1 min). The effects of a range of doses (0-1 mg kg-1) of the 5-HT3 receptor antagonists ondansetron, bemesetron, granisetron and tropisetron on hyperactivity induced by 0.6 mg kg-1 nicotine were then assessed. Only tropisetron at 1 mg kg-1 attenuated nicotine-induced hyperactivity. To demonstrate the efficacy of the present range of doses of the 5-HT3 receptor antagonists in this study, conditioned taste aversion experiments were conducted. Ondansetron (0.1 mg kg-1) failed to attenuate a conditioned taste aversion to saccharin induced by nicotine (0.6 mg kg-1), but did induce a reduction in saccharin preference in choice tests following three saccharin-ondansetron pairings.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract

The effects of desipramine, tranylcypromine, and phenelzine on beta-adrenoceptor subtype binding were measured in rat cerebral cortex and cerebellum. The drugs were administered to male Sprague Dawley rats for 28 d sc via 2ML4 Alzet osmotic minipumps (desipramine HCl 10, tranylcypromine HCl 1, phenelzine sulfate 5, 10 mg kg-1/d). Binding of [3H]CGP 12177 was measured to determine total beta-adrenoceptor density in each brain region. The relative densities of beta 1- and beta 2-adrenoceptors were directly calculated from competition analysis using ICI 89406 to displace [3H]CGP 12177. beta 1-Adrenoceptor density was decreased in cortical tissue following each antidepressant treatment, but no effects on beta 2-adrenoceptor density were evident. With cerebellar tissue, despite a higher density of beta 2-adrenoceptors in this area, no effects of antidepressants on beta 2-adrenoceptor density were evident. The present data confirm and extend previous reports of beta 1- but not beta 2-adrenoceptor downregulation in brain following chronic antidepressant drug treatment.

No abstract

No abstract