Effects of d-amphetamine and disruption of 5-hydroxytryptaminergic neuronal systems on the synthesis of dopamine in selected regions of the rat brain.

Abstract

The rate of accumulation of DOPA following the administration of a decarboxylase inhibitor was employed to estimate the in vivo rate of dopamine (DA) synthesis in rat brain regions containing the cell bodies (substantia nigra) and terminals (striatum) of nigrostriatal nerves, and the terminals of mesolimbic (nucleus accumbens, olfactory tubercle) and tuberoinfundibular (median eminence) nerves. d-Amphetamine (0.5–2 mg/kg, i.p.) caused a marked increase in DA synthesis in striatum, a modest increase in olfactory tubercle, and was without effect in nucleus accumbens and median eminence. At the largest dose, f-amphetamine slightly reduced DA synthesis in substantia nigra. The mechanism of these regional differences is currently unknown. Depletion of 5-hydroxytryptamine (5-HT) with an intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) or a systemic injection of p-chlorophenylalanine (pCPA) enhanced spontaneous and amphetamine-stimulated locomotor activity. Pretreatment with 5,7-DHT did not alter DOPA accumulation in any brain region of animals injected with d-amphetamine or its vehicle. Pretreatment with pCPA reduced DOPA accumulation only in regions containing terminals of mesolimbic DA nerves. Thus, the increased amphetamine-induced hyperactivity in 5-HT-depleted rats is not reflected in a consistent change in the rate of DA synthesis in the brains of these animals.