A simple and rapid method for assessing similarities among directly observable behavioral effects of drugs: PCP-like effects of 2-amino-5-phosphonovalerate in rats.

Directly observable behavioral effects of the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (AP5) (10-1,000 mg/kg IP, 0.18-5.6 mumol/rat ICV) and of phencyclidine (PCP) (3.2-56 mg/kg IP, 0.032-3.2 mg/rat ICV), ketamine (10-100 mg/kg), amphetamine (1-18 mg/kg), apomorphine (0.1-5.6 mg/kg), chlordiazepoxide (1-100 mg/kg), and pentobarbital (3.2-56 mg/kg) were studied in rats. Pharmacologically specific results were obtained rapidly and reliably, using a cumulative dosing procedure. Cluster analysis grouped the drug treatments, on the basis of their similarities in producing different behavioral activities, into three main clusters; characteristically, stimulant drugs (amphetamine, apomorphine) produced sniffing and gnawing; PCP-like drugs (PCP, ketamine) produced locomotion, sniffing, swaying and falling; sedative drugs (pentobarbital, chlordiazepoxide) produced loss of righting. The behavioral effects of ICV administration of AP5 were more similar to the effects of PCP-like drugs than to the effects of either stimulant or sedative drugs, thus supporting the hypothesis that the behavioral effects of PCP-like drugs may result from reduced neurotransmission at excitatory synapses utilizing NMDA preferring receptors. The present procedure is simple, rapid and may provide a useful approach in the classification of behaviorally active drugs.