IN-VIVO REGULATION OF DOPA DECARBOXYLASE BY DOPAMINE-RECEPTORS IN RAT-BRAIN

To test the hypothesis that dopamine (DA) receptors influence cerebral DOPA-decarboxylase (DDC) activity in vivo, we used HPLC to measure th e kinetics of the cerebral uptake and metabolism of [H-3]DOPA in carbi dopa-treated rats, and in rats also treated acutely with a DA receptor antagonist (flupenthixol, 2 mg/kg, intraperitoneally) or a DA recepto r agonist (apomorphine, 200 mu g/g, subcutaneously). The unidirectiona l blood-brain clearance of [H-3]DOPA (K-1(DOPA), 0.030 mL g(-1) min(-1 )) increased by 50% after flupenthixol. The magnitudes of the relative DDC activity (k(3)(DOPA)) in striatum (0.20 min(-1)), olfactory tuber cle (0.11 min(-1)), and hypothalamus (0.15 min(-1)) of carbidopa-treat ed rats were doubled with flupenthixol, but cortical DDC activity was unaffected (0.02 min(-1)). Apomorphine reduced the magnitude of k(3)(D OPA) in striatum by 20%. The rate constant for catabolism of [H-3]DA f ormed in brain (k(7)', monoamine oxidase [MAO] activity), which ranged from 0.025 min(-1) in striatum to 0.08 min(-1) in hypothalamus of car bidopa-treated rats, globally increased 2- to 4-fold after flupenthixo l, and decreased to 0.003 min(-1) in striatum after apomorphine. These in vivo results confirm the claim that acute blockade of DA receptors with flupenthixol stimulates the synthesis of [H-3]DA from [H-3]DOPA, and that this [H-3]DA is subject to accelerated catabolism. Conversel y, activation of the DA receptors with apomorphine inhibits DDC activi ty and DA catabolism.