N-methyl-D-aspartate receptor antagonists enhance the head-twitch response, a 5-hydroxytryptamine₂ receptor-mediated behaviour, in reserpine-treated mice

In this study, N-methyl-D-aspartate (NMDA)-receptor antagonists enhanced the head-twitch response induced by 5-hydroxytryptamine (5-HT) in reserpine-treated mice. To minimize the risk of any indirect involvement of NMDA-receptor antagonists (D(-)-2-amino-5-phosphonopentanoic acid (AP-5), D(-)-3(2-carboxypiperazine-4-yl)-propyl-l-phosphonic acid (CPP), (+)-5-methyl-10,11-dihydroxy-5H-dibenzo-[a,d]-cyclohepten-5,10-imine (MK-801), ketamine, dextrorphan and dextromethorpan) with 5-HT neurones, vesicle stores of monoamines, especially 5-HT, were depleted with reserpine. In addition, the enhancement of 5-HT-induced head-twitch response was inhibited by apomorphine and NMDA as well as ritanserin in reserpine-treated mice. These results support our previous conclusion that NMDA receptors play important roles in the glutamatergic modulation of 5-HTergic function at the postsynaptic 5-HT₂ receptors in mice.