Comparison of 2, 5-dimethoxy-4-methylamphetamine (DOM) and d-amphetamine for in vivo efflux of catecholamines from rat brain.

The neurochemical effects of DOM and d-amphetamine were compared under several conditions in unanesthetized rats implanted with chronic-indwelling push-pull cannulae in a cerebral lateral ventricle. Brain catecholamine storage sites were previously pulse-labelled with 14-C-norepinephrine administered intraventricularly. During the perfusion of the lateral ventricles with artificial cerebrospinal fluid, the animals were injected i.p. with 1.5 mg/kg of DOM, 2.0 mg/kg of d-amphetamine or 1.0 ml/kg of isotonic saline. Analysis of the perfusate in successive samples indicated an increased efflux of 14-C-radioactivity in rats administered DOM or d-amphetamine. Increased proportions of 14-C-norepinephrine and 14-C-normetanephrine were detected in samples of perfusate 15 to 30 min after drug injection. Pretreatment of other animals with 6-hydroxydopamine intraventricularly, which decreased brain levels of both norepinephrine and dopamine, blocked the increased efflux of 14-C-radioactivity induced by DOM or d-amphetamine. Pretreatment of rats with 6-hydroxydopa i.p., which depleted brain norepinephrine selectively, reduced to about half the d-amphetamine-induced efflux of 14-C-radioactivity for all samples during the time course of the effect. However, animals pretreated with 6-hydroxydopa and then tested for DOM effects showed a different pattern of 14-C-radioactivity efflux. The efflux for the initial samples was increased as with the DOM control, but the 6-hydroxydopa pretreatment attuated the DOM-induced efflux for the later samples. The results suggest DOM and d-amphetamine share qualitatively similar effects in releasing and/or blocking the reuptake of catecholamines at brain periventricular nerve terminals. Nevertheless, DOM appears to differ from d-amphetamine in the temporal pattern of net catecholamine release.