Chronic cocaine administration decreases dopamine synthesis rate and increases [3H] spiroperidol binding in rat brain

Abstract Chronic administration of cocaine HC1 (10 mg/kg, IP, every 12 hours for 10 consecutive days) resulted in a significantly decreased rate of accumulation of 3,4-dihydroxyphenylalanine following decarboxylase inhibition (−27 to −33%) and of homovanillic acid following probenecid treatment (−25 to −34%) in rat striatum, limbic forebrain and midbrain. In addition, the B max i for [ 3 H]spiroperidol receptor binding was significantly increased (+24 to +36%) in these brain regions following chronic cocaine administration. These changes were observed 60 days following termination of the chronic cocaine treatment regimen. These data suggest that cocaine produces long-term, if not permanent, effects on central dopamine synthesis.