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/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 also enhanced the cataleptogenic action of haloperidol, with many rats being spontaneously cataleptic after apomorphine withdrawal. It is suggested that the reduced 3H-apomorphine binding signifies less presynaptic receptors. This permits less autoregulation and enhanced dopamine agonist action, possibly accounting for the dopaminergic sensitization by long-term agonists.
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D008297:Male; D011485:Protein Binding; D011869:Radioligand Assay; D051381:Rats; D013569:Synapses / Q000502:physiology*
D000661:Amphetamine; D001058:Apomorphine; D004298:Dopamine