Eight μg of 6-hydroxydopamine (6-OHDA) injected bilaterally into the nucleus accumbens septi (NAS) or the caudate nucleus of the rat resulted in 79% and 50% depletion of endogenous dopamine (DA) at these respective sites. Fourteen days after the injection a low dose of amphetamine failed to induce the characteristic locomotor response in the NAS-lesioned rats but did so in the caudate-lesioned animals. By contrast the caudate lesion, but not the NAS lesion, abolished intense forms of stereotyped behaviour induced by higher doses of amphetamine. Both lesioned groups exhibited supersensitivity to the dopamine agonist, apomorphine; the NAS group showed enhanced locomotor activity and the caudate group enhanced stereotyped behaviour. The block of amphetamine locomotion and the enhanced response to apomorphine were maximal around 14 days after the operation and gradually attenuated up to 90 days. There is evidence that remaining DA levels in the NAS are greater at 90 than at 14 days postoperatively. Thus recovery of behavioural effects correlated with an increase in the remaining levels of DA in the NAS.
Article abstract: The author reviews the impact of a paper published 40 years ago which was among the first to localise the different behavioural actions of amphetamine in rats to specific brain regions, using local 6-hydroxydopamine-induced lesions of dopaminergic pathways This article is part of a Special Issue entitled SI:50th Anniversary Issue.
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