Comparison of the behavioral and biochemical effects of the NMDA receptor antagonists, MK-801 and phencyclidine.
The behavioral and biochemical effects of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 [+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate) were compared with those of phencyclidine (PCP). In the dose range used in this study, MK-801 (0.125-0.5 mg/kg i.p.) produced ataxia and other behavioral responses which were similar to PCP (5-10 mg/kg i.p.). However, turning and backpedalling induced by MK-801 were not dose-dependent and less intense at the dose producing approximately the same level of ataxia as PCP. Neurochemically, MK-801 (0.5 mg/kg i.p.) increased dopamine turnover in the cortex and striatum, but had no effect on 5-HT systems. It was also 3.4 times less potent in inhibiting 5-HT uptake than PCP. These results suggest that the behavioral responses induced by MK-801 involve primarily the PCP receptor and the dopamine system, and that the differences from PCP reflect a reduced effect on the 5-HT neuronal system.
Hiramatsu
M
M
Department of Pharmacology, University of California Los Angeles, School of Medicine 90024-1735.
Cho
A K
AK
Nabeshima
T
T
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001259:Ataxia / Q000139:chemically induced; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D012701:Serotonin / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects; D013997:Time Factors
D000927:Anticonvulsants; D015306:Biogenic Monoamines; D003986:Dibenzocycloheptenes; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D012701:Serotonin; D016291:Dizocilpine Maleate; D010622:Phencyclidine