NMDA receptor antagonists inhibit apomorphine-induced climbing behavior not only in intact mice but also in reserpine-treated mice

Abstract

The present study showed that the noncompetitive N-methyl- d-aspartate (NMDA) receptor antagonists, MK-801 {(+)-5-methyl-10,11-dihydroxy-5H-dibenzo-[a,d]-cyclohepten-5,10-imine hydrogen maleate}, ketamine, dextrorphan and dextromethorphan attenuated apomorphine-induced climbing behavior in reserpine-treated mice. In addition, the competitive NMDA receptor antagonists, d(−)-2-amino-5-phosphonopentanoic acid (AP-5) and d(−)-3-(2-carboxypipera-zine-4-yl)-propyl-1-phosphonic acid (CPP), also inhibited the apomorphine-induced climbing behavior in reserpine-treated mice as well as in intact mice. Previous work in our laboratory had shown that the noncompetitive NMDA receptor antagonists, MK-801, ketamine, dextrorphan and dextromethorphan cause a pronounced inhibition of apomorphine-induced cage climbing behavior in intact mice, suggesting the involvement of NMDA receptors in the glutamatergic modulation of dopaminergic function at the postsynaptic dopamine (DA) receptors. Therefore, the present results strongly support our previous conclusion that the NMDA receptors play important roles in the glutamatergic modulation of dopaminergic function at the postsynaptic DA receptors.