NMDA receptor antagonists enhance 5-HT2 receptor-mediated behavior, head-twitch response, in PCPA-treated mice.
Previous work in our laboratory has shown that the N-methyl-D-aspartate (NMDA) receptor antagonists, AP-5, CPP, MK-801, ketamine, dextrorphan and dextromethorphan cause a pronounced enhancement of 5-hydroxytryptamine (5-HT)-induced head-twitch response (HTR) in intact mice, suggesting the involvement of NMDA receptors in the glutamatergic modulation of serotonergic function at the postsynaptic 5-HT2 receptors. The purpose of this study was to extend our previous work on the behavioral interaction between glutamatergic and serotonergic receptors. In the present study, both competitive (AP-5 and CPP) and noncompetitive (MK-801, ketamine, dextrorphan and dextromethorphan) NMDA receptor antagonists markedly enhanced 5-HT-induced selective serotonergic behavior, HTR, in p-chlorophenylalanine (PCPA)-treated mice which were devoid of any involvement of indirect serotonergic function, to establish the involvement of the NMDA receptor in 5-HT-induced HTR at the postsynaptic 5-HT2 receptors. In addition, the enhancement of 5-HT-induced HTR was inhibited by a dopamine agonist, apomorphine, NMDA receptor antagonist, NMDA and a serotonin 5-HT2 receptor antagonist, cyproheptadine, in PCPA-treated mice. Therefore, the present results support our previous conclusion that the NMDA receptors play an important role in the glutamatergic modulation of serotonergic function at the postsynaptic 5-HT2 receptors.
Kim
H S
HS
College of Pharmacy, Chungbuk National University, Cheongju, Korea.
Park
I S
IS
Lim
H K
HK
Choi
H S
HS
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D010134:Fenclonine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D014365:Tryptophan Hydroxylase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D012701:Serotonin; D014365:Tryptophan Hydroxylase; D010134:Fenclonine