Differential potentiation of L-tryptophan-induced head-twitch response in mice by cocaine and sertraline.
Using selective monoamine uptake blockers and appropriate selective monoamine receptor antagonists, we have previously shown that cocaine enhances the frequency of 5-HT2A receptor-mediated 5-hydroxytryptophan (5-HTP)-induced head-twitch response (HTR) in mice via inhibition of serotonin uptake. Concomitantly, cocaine prevented the maximal producible HTR frequency via simultaneous indirect stimulation of the inhibitory presynaptic 5-HT1A and postsynaptic alpha 2 receptors. In the present study, we have investigated the effects of cocaine and the selective 5-HT (sertraline), norepinephrine (nisoxetine) and dopamine (GBR 12935) uptake inhibitors on the L-tryptophan-induced HTR in the presence of a nonselective monoamine oxidase inhibitor, tranylcypromine. We utilized two experimental protocols where cocaine or sertraline were administered either after (protocol 1) or prior to (protocol 2) L-tryptophan injection. Cocaine potentiated the ability of L-tryptophan to induce HTR to a greater extent in protocol 1, whereas sertraline induced a greater effect in protocol 2. However, in our earlier study cocaine (and also sertraline) up to 10 mg/kg produced a similar degree of potentiation in both experimental protocols on the 5-HTP-induced HTR. Furthermore, as in the latter study on the 5-HTP-induced HTR, in the present investigation nisoxetine potently attenuated whereas GBR 12935 did not modulate the induced HTR. The results show that the respective serotonergic and noradrenergic effects of cocaine also operate on the L-tryptophan-induced HTR. The differential effects of cocaine and sertraline in experimental protocols 1 and 2 on the L-tryptophan- versus 5-HTP-induced HTRs suggest that cocaine has additional effects on the conversion of L-tryptophan to 5-HT.
Darmani
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Department of Pharmacology Kirksville College of Osteopathic Medicine, MO 63501, USA.
D015057:1-Naphthylamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005473:Fluoxetine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D019416:Head Movements / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D020280:Sertraline; D014364:Tryptophan / Q000008:administration & dosage / Q000494:pharmacology*
D015057:1-Naphthylamine; D003042:Cocaine; D005473:Fluoxetine; D009638:Norepinephrine; D010879:Piperazines; D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D014364:Tryptophan; C011386:nisoxetine; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine