Behavioral effects of serotonergic and dopaminergic drugs in cats following chronic amphetamine administration.

Chronic administration of amphetamine to cats (twice daily, in doses increasing from 5 to 15 mg/kg over a 10-day period) elicited a number of behaviors e.g., limb flicking, abortive grooming, and excessive head shaking, which were originally proposed as an animal behavioral model for studying the actions of hallucinogens that depress central serotonergic neurotransmission. This drug treatment produced large decreases (approximately 50%) in central nervous system serotonin (5HT) and its major metabolite, 5-hydroxyindoleacetic acid, and even larger decreases (approximately 90%) in the levels of dopamine (DA) and norepinephrine. Administration of the 5HT precursors L-tryptophan (25 mg/kg i.p.) or L-5-hydroxytryptophan (12.5 mg/kg i.p.), a direct-acting 5HT agonist (quipazine, 1 mg/kg i.p.) or a monoamine oxidase inhibitor (tranylcypromine, 4 mg/kg i.p.) produced no significant changes in these behaviors in cats treated chronically with amphetamine. Administration of a 5HT reuptake blocker (fluoxetine, 5 mg/kg i.p.) produced a small, but significant, decrease in the frequency of occurrence of these behaviors in amphetamine-treated cats. L-Dihydroxyphenylalanine (L-DOPA, 20 mg/kg i.p.) greatly potentiated these behaviors in cats chronically treated with amphetamine, but L-DOPA was totally ineffective in eliciting these behaviors in naive animals. The behavioral effects of apomorphine (2 mg/kg i.p.) were also significantly potentiated by chronic amphetamine pretreatment. The amino acid precursor of DA, L-tyrosine (25 mg/kg i.p.), and a DA reuptake blocker, bupropion (5 mg/kg i.p.) were without significant effect on these behaviors in amphetamine-treated cats. The data suggest that these cat behaviors are elicited by an action at central DA receptors and that these receptors become supersensitive following chronic amphetamine administration. Furthermore, there may be a qualitative change in DA receptors, since L-DOPA is very effective in potentiating these behaviors in cats treated chronically with amphetamine, but is totally ineffective in naive cats.