Differentiaton of neuropharmacological actions of apomorphine and d-amphetamine

The dopaminergic agonists apomorphine and d-amphetamine elicit hyperthermic, hyperkinetic and stereotypic responses in the rabbit. The present investigation compares the influence exerted by various serotonergic antagonists upon these activities. Apomorphine-induced hyperthemia was antagonized by p-chlorophenylalanine (pCPA), cyproheptadine and cinanserin and was restored in pCPA-pretreated rabbits by regeneration of central serotonin levels, d-Amphetamine-induced hyperthermia was reduced by pCPA; restored in pCPA-pretreated animals by regeneration of central serotonin levels; and was uninfluenced by cyproheptadine and cinanserin. Apomorphine-induced locomotor stimulation was unaltered by serotonergic antagonists; however, these same doses of anti-serotonergic agents all markedly reduced d-amphetamine-induced hyperkinesia. Serotonergic antgaonists also failed to affect apomorphine-induced compulsive gnawing but did significantly enhance d-amphetamine-induced compulsive gnawing. It is concluded from these data that the neuropharmacological activities of apopmorphine and d-amphetamine in the rabbit differ in their dependence upon central serotonergic mechanisms.