Bupropion, d-amphetamine, and amitriptyline-induced conditioned taste aversion in rats: dose effects.

Nine groups of rats (n = 6 per group) were adapted to a daily one-half hour period of water availability. When intake had stabilized, they were allowed access to a 0.1% (w/v) solution of saccharin, and immediately afterward were given IP injections of isotonic saline; bupropion HCl (10.0, 20.0, or 40.0 mg/kg); d-amphetamine-sulfate (0.5, 1.0, 2.0 mg/kg); or amitriptyline HCl (5.0, 10.0, or 20.0 mg/kg) in a volume of 1 ml. The lowest dose of each compound as chosen to be equipotent in screening tests used to identify potential antidepressants. Following 2 days of access to water alone, all groups were given a choice between water and saccharin for 3 consecutive days. All compounds induced taste aversions in a dose-related manner, but amitriptyline induced greater and longer-lasting aversions than either bupropion or d-amphetamine which were equipotent over the dose range studied. As such, this is the first demonstration that bupropion and amitriptyline, two clinically effective antidepressants, can induce taste aversions and replicates as well the common finding that d-amphetamine has substantial taste aversion-inducing properties. The ability of these compounds to induce taste aversions could be mediated through their effects on central catecholaminergic processes although amitriptyline has significant peripheral anticholinergic effects.