RT Journal Article
SR Electronic
T1 Neurochemical effects of amphetamine metabolites on central dopaminergic and serotonergic systems.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 901
OP 908
VO 251
IS 3
A1 Matsuda, L A
A1 Hanson, G R
A1 Gibb, J W
YR 1989
UL http://jpet.aspetjournals.org/content/251/3/901.abstract
AB Intrastriatal administration of the hydroxylated metabolites of amphetamine, p-hydroxyamphetamine (p-OHA) or p-hydroxy-norephedrine (p-OHNor), decreased local concentrations of dopamine and serotonin in a dose-dependent manner. Although both compounds reduced concentrations of the metabolites of dopamine, 5-hydroxyindoleacetic acid concentrations were elevated. After systemic treatment with p-OHA, striatal dopamine was also reduced. In contrast, only hypothalamic and hippocampal serotonin stores were altered significantly in rats treated with p-OHA systemically. Neither compound decreased the activities of tryptophan hydroxylase or tyrosine hydroxylase. Because p-OHA is metabolized to p-OHNor via dopamine beta-hydroxylase present in noradrenergic neurons, the direct effects of these compounds on dopaminergic and serotonergic variables can be observed in rats which receive intrastriatal drug treatment. p-OHA and p-OHNor were equally potent in decreasing dopamine concentrations. However, p-OHNor was more potent than p-OHA in decreasing serotonin concentrations. Both compounds more readily depleted dopamine compared to serotonin stores. Complete recovery of p-OHA-induced decreases in striatal dopamine occurred within 48 hr of intrastriatal administration and concurrent treatment with the dopamine uptake blocker, amfonelic acid, significantly attenuated the p-OHA-induced effects on dopamine.