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NMDA receptor antagonists enhance 5-HT2 receptor-mediated behavior, head-twitch response, in PCPA-treated mice

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Abstract

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 noncompeti- tive (MK-801, ketamine, dextrorphan and dextromethorphan) NMDA receptor antagonists markedly enhanced 5-HT-induced selective serotonergic behavior, HTR, inp-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.

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  1. College of Pharmacy, Chungbuk National University, 361-763, Cheongju, Korea

    Hack-Seang Kim, In-Sook Park, Hwa-Kyung Lim & Hong-Seork Choi

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Kim, HS., Park, IS., Lim, HK. et al. NMDA receptor antagonists enhance 5-HT2 receptor-mediated behavior, head-twitch response, in PCPA-treated mice. Arch Pharm Res 22, 113–118 (1999). https://doi.org/10.1007/BF02976533

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  • DOI: https://doi.org/10.1007/BF02976533

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