Effects of dopaminergic agonists and antagonists of feeding in intact and 6-hydroxydopamine-treated rats.

The effects on food intake of treatments which alter central dopaminergic function were examined in rats. Doses of d-amphetamine that increased the conversion of 3H-tyrosine to 3H-dopamine in the brain were found to decrease food intake, an effect that was reduced by the systemic administration of the dopaminergic antagonists alpha-methyltyrosine, haloperidol or spiroperidol. The dopaminergic agonists, apomorphine, dopa, cocaine and methylphenidated, also reduced feeding and these effects were attenuated by low doses of spiroperidol. In larger doses, spiroperidol itself decreased feeding, and this effect was potentiated by alpha-methyltyrosine. The ability of dopaminergic agonists and antagonists to inhibit food intake was also observed in rats treated with 6-hhyroxydopamine so as to produce a selective 83% depletion of dopamine. In these animals, d-amphetamine was found to be less effective as an anorexic agent, whereas dopa, apomorphine, alpha-methyltyrosine and spiroperidol each was more effective in reducing food intake. These alterations in sensitivity may reflect neurochemical changes which occur at residual dopaminergic synapses after subtotal lesions of dopaminergic neurons. We conclude that both increases and decreases in central dopaminergic activity can reduce feeding and propose that some intermediate rate of dopamine release provides an optimal level of neuronal activity for feeding by the hungry animal.