The effect of chronic administration of d‐amphetamine on regional changes in catecholamines in the rat brain

Abstract

Abstract Changes in the dopamine, noradrenaline and dihydroxyphenylacetic acid (DOPAC) concentrations were determined in 6 regions of the rat brain following chronic amphetamine administration for 2 weeks and at intervals of up to 7 days after drug withdrawal. Chronic amphetamine administration caused pronounced stereotypy; following withdrawal the animals were behaviourally depressed for at least 7 days. The noradrenaline concentration of all brain areas investigated was decreased throughout most of the experimental period; only in the midbrain and the olfactory lobes did the noradrenaline concentration return to control values 7 days after drug withdrawal. In contrast, the dopamine concentration was raised in the midbrain, hippocampus, and olfactory lobes following drug administration but reduced in the striatum, brain stem, and amygdaloid cortex. Following amphetamine withdrawal, most of the brain areas showed a decrease in the dopamine concentration apart from the olfactory lobes which showed an increase and the midbrain and hippocampus which were largely unchanged. The concentrations of the intraneuronal metabolite DOPAC were decreased in most brain areas throughout the duration of the experiment, suggesting that the turnover of dopamine was decreased. These results are discussed with reference to the possible decreased activity in tyrosine hydroxylase both during drug treatment and after withdrawal.