Apomorphine lowers dopamine synthesis for up to 48 h: implications for drug sensitization

Previous reports have shown that tolerance or sensitization to apomorphine depends on the dosage interval. The effect of apomorphine on behaviour increases when there is a drug-free period between successive injections. Here we studied the biochemical action of apomorphine during a drug-free period. The experiments showed that dopamine level and dopamine turn-over are persistently inhibited for at least 48 h after apomorphine administration. At 24 h after drug injection, there was a decrease of both DOPAC level and tyrosine hydroxylase activity. The results suggest that apomorphine induces long-lasting dopaminergic inhibition action that increases drug-induced behavioural response, perhaps after development of postsynaptic hypersensitivity.