Effects of reinforcement-blocking doses of pimozide on neural systems driven by rewarding stimulation of the MFB: a 14C-2-deoxyglucose analysis.

An analysis by means of 14C-2-deoxyglucose autoradiography of the neural systems unilaterally activated by the reinforcing stimulation used in the two accompanying papers revealed strong and reliable effects in the nucleus of the diagonal band of Broca, in the medial forebrain bundle (MFB) and/or the fornix throughout the diencephalon, and in the part of the anterior ventral tegmentum where the dopaminergic projection to the lateral habenula originates. The terminal fields of the dopaminergic forebrain projections were not affected, but there was bilateral suppression of lateral habenular activity. A second experiment found that the same systems are still activated by (automatically administered) reinforcing stimulation in rats treated with reinforcement blocking doses of pimozide. The only clear effect of pimozide was to reverse the bilateral suppressive effect of the stimulation on lateral habenular activity. Animals treated with pimozide show greatly elevated activity in the lateral habenula, whether or not they receive reinforcing stimulation. The results suggest that pimozide's effect on reinforcement is mediated by the circuitry interconnecting the lateral habenula with the nucleus of the diagonal band of Broca and/or the anterior ventral tegmentum.