title: 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.
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D002552:Cerebral Ventricles; D002852:Chromatography, Ion Exchange; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D009411:Nerve Endings / Q000378:metabolism; D010477:Perfusion; D012110:Reserpine / Q000494:pharmacology; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism
chemical_list: D008781:Methyltyrosines; D014443:Tyrosine; D012110:Reserpine; D003913:Dextroamphetamine; D004298:Dopamine