A rapid method for evaluating the behavioral effects of phencyclidine-like dissociative anesthetics in mice.
A simple and rapid method for detecting the behavioral effects of phencyclidine and related dissociative anesthetics is described. Dissociative anesthetics such as phencyclidine (PCP) and dizolcipine, which bind with high affinities at N-methyl-D-aspartate (NMDA) coupled cation channels ("PCP receptors"), produced a dose-related increase in the percentage of mice that fell from a 1.5 cm deep circular arena mounted on a 60 cm platform. A similar behavior was not manifest by other classes of compounds examined including competitive NMDA antagonists, an antagonist at strychnine-insensitive glycine receptors, and sigma-receptor ligands with moderate to low affinities for PCP receptors. Pretreatment of mice with glycine reduced in a dose-dependent manner the percentage of falls elicited by a maximally effective dose of dizolcipine. This simple procedure may prove useful for both the rapid detection of dissociative anesthetics and evaluation of putative PCP antagonists.
Evoniuk
G E
GE
Laboratory of Neuroscience, NIDDK-LN, National Institutes of Health, Bethesda, MD 20892.
Hertzman
R P
RP
Skolnick
P
P
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004192:Discrimination, Psychological / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000494:pharmacology; D051379:Mice; D010622:Phencyclidine / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects; D017465:Receptors, Opioid, delta; D017478:Receptors, Phencyclidine
D000777:Anesthetics; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017478:Receptors, Phencyclidine; D016291:Dizocilpine Maleate; D010622:Phencyclidine; D005998:Glycine