NMDA receptor antagonists inhibit apomorphine-induced climbing behavior not only in intact mice but also in reserpine-treated mice.
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-im ine 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.
Kim
H S
HS
College of Pharmacy, Chungbuk National University, Cheongju, South Korea.
Rhee
G S
GS
Oh
S
S
Park
W K
WK
D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects*; D009433:Neural Inhibition / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012110:Reserpine / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D012110:Reserpine; D001058:Apomorphine