PRESYNAPTIC SUBSENSITIVITY AS A POSSIBLE BASIS FOR SENSITIZATION BY LONG-TERM DOPAMINE MIMETICS

A possible cellular basis for dopaminergic sensitization by long-term dopamine mimetics was examined in rat brain striatum. Long-term apomorphine or amphetamine administration (10 mg/kg per day for 14 days) resulted in a decrease in the specific binding of 3H-apomorphine, but no change in 3H-haloperidol binding. Long-term apomorphine treatment enhanced the cateleptogenic action of haloperidol, with many rats being spontaneously cataleptic after apomorphine withdrawal. The reduced 3H-apomorphine binding may signify less presynaptic receptors. This permits less autoregulation and enhanced dopamine agonist action, possibly accounting for the dopaminergic sensitization by long-term agonists.