Effects of chlorimipramine and protriptyline on the hyperactivity induced by 5-hydroxytryptophan after peripheral decarboxylase inhibition in mice

Summary DL-5-HTP in doses from 100 mg/kg is reported to increase the spontaneous motor activity in mice pretreated with L--hydrazino--methyl--(3, 4-dihydroxyphenyl)-propionic acid (MK-486), an inhibitor of peripheral aromatic aminoacid decarboxylase. Exogenously administered 5-HTP gives rise to accumulation of 5-HT in both central 5-HT-and catecholamine-neurons. The stimulant effect of DL-5-HTP may be mediated via increased activation of 5-HT receptors or, via displacement, increased activation of catecholamine receptors. In the present experiment pre-treatment with chlorimipramine, 25 mg/kg concomitant with MK-486 markedly potentiated the stimulant effect of DL-5-HTP on motor activity,i.e. the dose response curve was shifted to the left. DL-5-HTP, 75 mg/kg, induced in these animals a pronounced increase of the motor activity but had no significant effect on the brain concentrations of DA or NA. Pre-treatment with protriptyline-HCl, 25 mg/kg, concomitant with MK-486 did not potentiate the stimulant effect of DL-5-HTP. The results indicate that the DL-5-HTP induced motor activity is largely dependent on an increased activation of central 5-HT receptors.