D-amphetamine-induced release of "newly synthesized" and "stored" dopamine from the caudate nucleus in vivo

Abstract

The lateral and third ventricles of anesthetized cats were perfused continuously with artificial cerebrospinal fluid (CSF) containing 3H-tyrosine and the perfusate was analyzed for 3H-catecholamines. The addition of d-amphetamine sulfate to the perfusing CSF for 2 hours, beginning 2 hours after the start of the 3H-tyrosine perfusion, caused an immediate increase in the efflux of 3H-dopamine. The efflux of this amine declined subsequently despite the continued presence of amphetamine in the CSF. The addition of alpha-methyltyrosine to the CSF concurrently with the d-amphetamine did not markedly alter the immediate increase but accelerated the subsequent decline in the efflux of 3H-dopamine. This suggests that ampetamine initially releases dopamine from a "strong pool," but continuous release is dependent upon ongoing amine synthesis. The addition of d-amphetamine to the 3H-tyrosine containing CSF at the start of perfusion immediately increased the efflux of 3H-dopamine. This response was completely blocked by the presence of alpha-methyltyrosine in the CSF. Pretreatment of cats with reserpine effectively depleted the caudate nucleus of endogenous and 3H-dopamine, but did not alter the ability of d-amphetamine to increase the efflux of 3H-dopamine. Indeed, the amount of 3H-dopamine released during each collection period by either intraventricular or intravenous administration of d-amphetamine was higher than the content of the labeled amine remaining in the whole caudate nucleus. These results suggest that damphetamine can release both "stored" and "newly synthesized" 3H-dopamine from the caudate nucleus, but that the maintenance of the amphetamine-induced release of dopamine is dependent upon the newly synthetized pool.