Abstract

Considerable evidence implicates dopamine in brain stimulation reward. For example, dopamine antagonists or destruction of dopaminergic neurons reduce the reward effectiveness of medial forebrain bundle stimulation. Assessment of such effects is complicated by across-subject averaging and by motor deficits, which are thought to be due to destruction of dopaminergic projections to the dorsal striatum. In contrast, the changes in reward have been linked to changes in the dopaminergic input to the nucleus accumbens (NAcc). We reexamined the effects of dopamine depletion induced by 6-hydroxydopamine (6-OHDA) on lateral hypothalamic (LH) self-stimulation using within-subject analysis. To minimize motor deficits due to destruction of the dorsal striatal dopaminergic input, I made multiple injections of 6-OHDA (totaling 9.6 og/6 ol/side) into the NAcc by means of glass micropipettes. Frequency thresholds for LH self-stimulation were measured before and after 6-OHDA injection. Dopamine was depleted by 55-92% in the NAcc, and by 0-52% in the dorsal striatum. Seven of 13 rats showed no threshold changes, four showed modest threshold increases and two showed threshold decreases. In one rat, unilateral 6-OHDA treatment caused bilateral threshold increases. Maximum post-lesion response rates were 20-80% of baseline values. Surprisingly, threshold changes were uncorrelated with dopamine depletion. The present study adds a paradox concerning the role of NAcc DA in BSR.