Dopaminergic mediation of the interoceptive cue produced by d-amphetamine in rats

After rats were trained to differentiate between the effects of d-amphetamine and saline in a state-dependent task, pretreatment with the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine, significantly decreased amphetamine discrimination. Pretreatment with the dopamine-beta-hydroxylase inhibitor, disulfiram, or with the tryptophan hydroxylase inhibitor, p-chloro-phenylalanine, was observed to have no effect on the rats' ability to discriminate d-amphetamine. Administration of haloperidol, a selective dopamine receptor blocker, completely abolished the amphetamine discrimination, whereas alpha- and beta-adrenergic receptor blockade had no effect. Apomorphine, a dopamine receptor stimulant, produced amphetamine-like responses and this was, likewise, abolished by pretreatment with haloperidol. These data suggest that dopaminergic systems mediate the interoceptive cue produced by d-amphetamine in rats, and these results are discussed in relation to possible dopamine mediation of amphetamine psychosis and paranoid schizophrenia.