DIFFERENTIAL POTENTIATION OF L-TRYPTOPHAN-INDUCED HEAD-TWITCH RESPONSE IN MICE BY COCAINE AND SERTRALINE

Using selective monoamine uptake blockers and appropriate selective mo noamine receptor antagonists, we have previously shown that cocaine en hances the frequency of 5-HT2A receptor-mediated 5-hydroxytryptophan ( 5-HTP)-induced head-twitch response (HTR) in mice via inhibition of se rotonin uptake. Concomitantly, cocaine prevented the maximal producibl e HTR frequency via simultaneous indirect stimulation of the inhibitor y presynaptic 5-HT,, and postsynaptic alpha(2) receptors. In the prese nt study, we have investigated the effects of cocaine and the selectiv e 5-HT (sertraline), norepinephrine (nisoxetine) and dopamine (GBR 129 35) uptake inhibitors on the L-tryptophan-induced HTR in the presence of a nonselective monoamine oxidase inhibitor, tranylcypromine. We uti lized two experimental protocols where cocaine or sertraline were admi nistered either after (protocol 1) or prior to (protocol 2) L-tryptoph an injection. Cocaine potentiated the ability of L-tryptophan to induc e HTR to a greater extent in protocol 1, whereas sertraline induced a greater effect in protocol 2. However, in our earlier study cocaine (a nd also sertraline) up to 10 mg/kg produced a similar degree of potent iation in both experimental protocols on the 5-HTP-induced HTR. Furthe rmore, as in the latter study on the 5-HTP-induced HTR, in the present investigation nisoxetine potently attenuated whereas GBR 12935 did no t modulate the induced HTR. The results show that the respective serot onergic and noradrenergic effects of cocaine also operate on the L-try ptophan-induced HTR. The differential effects of cocaine and sertralin e in experimental protocols 1 and 2 on the L-tryptophan- versus 5-HTP- induced HTRs suggest that cocaine has additional effects on the conver sion of L-tryptophan to 5-HT.