Monoamine involvement in hippocampal self-stimulation.

The roles of noradrenergic and serotonergic projections to the hippocampus were investigated with respect to their involvement in the intracranial self-stimulation of this structure. In the first study, 6-hydroxydopamine-induced lesions of the dorsal tegmental noradrenergic bundle, which depleted hippocampal NE by 97%, had no effect on hippocampal self-stimulation in rats. In the second study, intragastric administration of para-chlorophenylalanine (PCPA) decreased hippocampal self-stimulation, suggesting the importance of a serotonin input in maintaining this behavior. Identical PCPA treatments resulted in temporary depletions of brain serotonin which paralleled the changes in hippocampal self-stimulation. The maximal decreases in both the biochemical and behavioral measures occured at 4 days post-drug. Interpretations of this deficit in hippocampal self-stimulation in terms of gross sensory and/or motor changes were ruled out as animals with lateral hypothalamic electrodes showed increases in self-stimulation paralleling the post-drug serotonin changes. An intra-sessional analysis of the PCPA-induced behavioral changes revealed that lateral hypothalamic self-stimulation was facilitated mainly during the first hour of the two-hour test sessions, whereas the depression in hippocampal self-stimulation occurred primarily in the last hour of the sessions. The differential effects of PCPA on lateral hypothalamic and hippocampal self-stimulation provide evidence against simple monoamine theories of reinforcement.