Effects of Acute and Chronic Amphetamine Intoxication on Brain Catecholamines in the Guinea Pig*

Abstract

A bstract: The effects of amphetamine on central and peripheral catecholamines have been studied in guinea pigs, since in this species, unlike several others, amphetamine is not metabolized by p-hydroxylation. Twenty mg/kg of dl-amphetamine-sulphate given intraperitoneally caused a 40 % decrease in brain and heart noradrenaline, a 13 % decrease in brain dopamine and a 60 % decrease in homovanillic acid in the caudate nucleus, four hours after its administration. The changes in tissue catecholamine levels and the increase in motor activity followed the time-course of the amphetamine concentrations both in the brain and plasma. After chronic administration of amphetamine at 12 hourly intervals for 7 or 18 days, there was a further decrease in brain and heart catecholamine and homovanillic acid levels. A 4-fold increase in the 3-0-methylated metabolites of noradrenaline and dopamine in brain after the administration of amphetamine to guinea pigs pretreated with nialamide and an increase in the urinary excretion of NA (13-fold) and adrenaline (3-fold) provided evidence for an amphetamine induced release of central and peripheral catecholamines as has previously been reported in rats and cats. Amphetamine disappeared from brain and plasma with an apparent half-life of 2.5-3.1 hours. Only amphetamine and hippuric acid were recovered in the urine after the administration of radioactively labelled amphetamine. No p-or (3-hydroxylated metabolites of amphetamine were present in the brain or heart tissues in the guinea pig. The results show that acute and chronic amphetamine administration cauSes changes in endogenous catecholamines in guinea-pigs similar to those found previously in rats in spite of differences in the metabolism of amphetamine between the two species.