Effect of tryptamine antagonists on self-stimulation. Interaction with amphetamine.

In order to investigate the role played by serotonergic mechanisms in self-stimulation (SS) behavior, the effects of two tryptamine antagonists, cyproheptadine and methysergide on SS were measured. Also the influence of antitryptaminic drug pre-treatment on the facilitatory effect of amphetamine, a pro-adrenergic drug, on SS was studied. Rats with brain electrodes permanently implanted at the lateral hypothalamus and trained to lever-press for response-contingent brain electric stimulus presentation were used. Stimulus current was maintained at threshold level. Both tryptamine antagonists used potentiated the enhancing effect of amphetamine on low SS rates, displacing to the left its dose-effect curve; cyproheptadine was at least three times more potent than methysergide. In addition, cyproheptadine, but not methysergide, caused dose-related increases in SS rate, when given alone. These results suggest that brain serotonergic systems play an inhibitory role in SS, opposing the facilitatory influence of adrenergic mechanisms.