Possible Interaction: Apomorphine and Cocaine

“In two experiments, behavior induced by apomorphine was potentiated during the initial post-injection period following a course of repeated, daily administrations of d-amphetamine or cocaine , suggesting the development of supersensitive dopaminergic post-synaptic mechanisms.”

“Moreover, animals pretreated with cocaine showed a significant (p<0.01) decrease in locomotor activity (LA) after a presynaptic, autoregulating dose of apomorphine (0.03 mg/kg sc) was given.”

“Recently it was shown that the combined pretreatment with low autoreceptor preferring dose levels of apomorphine (0.05 mg/kg) and 8-OHDPAT (0.05 mg/kg), which decrease dopaminergic and serotonergic activity, induces a profound behavioral inhibition and also blocks the stimulant effects of cocaine.”

“Initially, the 8OH and APO pretreatments prevented the locomotor stimulant effects of cocaine ; but, these inhibitory effects were reversed in the paired groups with repeated cocaine treatments, consistent with the emergence of cocaine sensitization effects.”

“At the 0.05 mg/kg dose level, the drug treatments given separately blocked cocaine induced increases in activity and the 8OH and APO inhibitory effects were again additive.”

“Moreover the relative potencies of these and other D2-like dopamine agonists (lisuride, 7-OH-DPAT, quinpirole, apomorphine , bromocriptine) to modulate cocaine self-administration were highly correlated with their relative potencies for increasing mitogenesis in vitro in cell lines expressing D3 but not D2 receptors.”

“When apomorphine was administered before cocaine , but not when administered before fencamfamine or amphetamine, distinctive changes occurred.”

“When 0.05 mg/kg apomorphine and 10 mg/kg cocaine were administered simultaneously, rotation appropriate for apomorphine resulted.”

“Thus cocaine , nomifensine and d-amphetamine increase 3-MT concentrations while gamma-butyrolactone, alpha-methyltyrosine and apomorphine decrease it.”

“This would suggest either that only quinpirole and apomorphine are effective in amplifying the conditioned effects of cocaine on Day 2 or that the cues produced by these drugs are more similar to those produced by cocaine than those produced by D1 agonists.”