Comparative effects of infusions of 6-hydroxydopamine into nucleus accumbens and anterolateral hypothalamus induced by 6-hydroxydopamine on the response to dopamine agonists, body weight, locomotor activity and measures of exploration in the rat.

Groups of rats received infusions of 6-hydroxydopamine (6-OHDA) into the nucleus accumbens or anterolateral hypothalamus with 6-hydroxydopamine (6-OHDA), or sham operations. Body weight was monitored for 28 days after the infusion, after which rats were first tested in an exploration choice-box and then underwent a series of pharmacological challenges. At this time after the operation, rats which had received 6-OHDA in the nucleus accumbens showed neither loss of body weight, deficit in exploration, nor hypokinesia, but sustained an 80% reduction in dopamine levels in the nucleus accumbens. Locomotion was decreased in response to 1.5 mg/kg (i.p.) of d-amphetamine but increased following 0.1 mg/kg (s.c.) of apomorphine; stereotyped responses to larger doses were unaltered. By contrast, rats which had received 6-OHDA in the anterolateral hypothalamus lesions lost substantial amounts of body weight and were hypoactive. Although both locomotor and stereotypy responses to d-amphetamine were abolished, these responses were enhanced in response to apomorphine. Consistent with this, regional assay using high pressure liquid chromatography (HPLC) showed profound loss of dopamine in the caudate-putamen as well as in the nucleus accumbens and frontal cortex. It seems unlikely that the reductions in exploration previously reported after lesions of the mesolimbicocortical dopamine system at the level of anterolateral hypothalamus induced by 6-OHDA are either behaviourally specific or result solely from depletion of dopamine with the nucleus accumbens and frontal cortex.