A role for dopamine in the psychopharmacology of electrical self-stimulation

The psychopharmacology of electrical self-stimulation of the lateral hypothalamus was studied using 6-hydroxydopamine, alpha-methyltyrosine, U-14, 624, and d-amphetamine. Reduction of brain dopamine, but not norepinephrine, with 6-hydroxydopamine produced an acute depression of responding which eventually recovered to pretreatment levels. A low dose of alpha-methyltyrosine, which did not affect responding in control rats, significantly depressed responding in the rats with brain dopamine reduced. This treatment did not alter responding of rats with norepinephrine reduced by 6-hydroxydopamine. A dopamine-beta-hydroxylase inhibitor, U-14, 624, depleted norepinephrine an additional 70% yet failed to alter self-stimulation in any of the groups. In other experiments, the 6-hydroxydopamine treatment which reduced brain dopamine was found to block the facilitation of self-stimulation produced by d-amphetamine. This facilitation of lateral hypothalmic self-stimulation was not influenced by treatments which reduced brain norepinephrine. An experiment suggesting that dopamine is of importance to locus coeruleus self-stimulation is also described. Implications of these data indicating a role for dopamine in self-stimulation responding are discussed in relation to the "catecholamine hypothesis of self-stimulation".