Effects of chronic amphetamine intoxication on the accumulation in the rat brain of labelled catecholamines synthesized from circulating tyrosine-14C and dopa-3H

Summary Accumulation of labelled noradrenaline (NA) and dopamine (DA) and endogenous levels of NA and DA in brain and heart were measured after infusion of tyrosine-¹⁴C and dopa-³H in rats. After a single dose of 20 mg/kg i.p. of dl-amphetamine sulphate a 50–65% decrease in the NA accumulation in the brain and heart was observed. The accumulation of DA was not changed. In rats treated chronically with amphetamine sulphate, 16–32 mg/kg i.p. twice daily for 4 weeks, both the brain and heart NA and brain DA levels were depleted by 40–70% at 20–24 h after amphetamine withdrawal. The accumulation of labelled NA and DA in these animals was not different from that of saline treated controls. When amphetamine sulphate, 20 mg/kg i.p., was given to chronically amphetamine treated rats there was a 45–60% decrease in the accumulation of labelled NA; labelled DA remained unchanged. It is concluded that the decrease in NA accumulation under acute and chronic amphetamine intoxication is most likely due to a preferential release of newly synthesized NA.The skilful technical assistance of Mrs Inger Jansson is gratefully acknowledged. A sample of 3-methoxytyrosine was generously supplied by AB Hässle, Mölndal, Sweden. The study was supported by the Swedish Medical Research Council (Project B71-14X-1017-07 and B71-27P-2627-03) and the Tri-Centennial Fund of the Bank of Sweden (Project Nr. 150).