The competitive NMDA antagonists CGP 43487 and APV potentiate dopaminergic function.
The administration to rats of different doses of the non competitive NMDA receptor blocker MK-801 (0.03-1 mg/kg IP) induced stimulation or reduction of locomotor activity, depending on the dose, whereas the competitive NMDA antagonists CGP 43487 (0.188-6 mg/kg IP) and APV (2.5-20 micrograms/rat ICV) inhibited locomotion at the highest doses. Unlike MK-801 and APV treatment, the administration of CGP 43487 did not induce impairment of rota-rod test performance. Both competitive and non-competitive NMDA antagonists, at doses devoid of any behavioral effect per se, potentiated the responses elicited by apomorphine (0.25 mg/kg SC). In particular, the occurrence of episodes of licking was weakly affected by MK-801 administration, but significantly increased by CGP 43487 and APV treatment; the presence of gnawing was augmented by all the pretreatments; sniffing, locomotion, grooming and rearing occurrence were not affected by the administration of NMDA antagonists. The results suggest that the competitive antagonists which facilitated dopaminergic function without causing motor impairment could be useful supplements in the treatment of Parkinson's disease.
Dall'Olio
R
R
Department of Pharmacology, University of Bologna, Italy.
Rimondini
R
R
Gandolfi
O
O
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; C087755:CGP 43487; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate