Differentiation between MK-801- and apomorphine-induced stereotyped behaviors in mice.

MK-801, a high-affinity analogue of phencyclidine (PCP), was given to mice to stimulate behaviors resembling those seen in schizophrenia. Apomorphine, a dopamine agonist, was also given to a separate group of mice for comparison. Visual observation showed that apomorphine caused intense gnawing and sniffing, while MK-801 did not produce gnawing. Automated measurements revealed frequent differences between the behaviors induced by the two drugs. The authors suggest that a compound which reduces PCP-stimulated behaviors but not apomorphine-stimulated ones might be an effective antipsychotic with fewer side effects than current dopamine-blocking drugs.

Study at a glance

Abstract

The ability of phencyclidine (PCP) to model schizophreniform psychosis is believed to be related to its ability to produce both hypoglutamatergia and hyperdopaminergia. As such, identification of PCP-stimulated behaviors may be important for the development of animal models of schizophrenia. In this study, MK-801 [(+)-5-methyl-10,11-dihydro-5H- dibenzo[a,d]cycloheptane-5,10-imine maleate], a high-affinity PCP analogue, was administered to mice in order to stimulate "PCP behaviors." These PCP behaviors were compared with behaviors stimulated by apomorphine, a dopamine agonist. Stereotyped behavior was assessed by both visual observations and automated measurements. Visual observations showed highly intense gnawing and sniffing in apomorphine-treated mice and the absence of gnawing in MK-801-treated mice. Automated stereotypic measures showed that, compared with vehicle-treated controls, there were frequent dissociations between MK-801 and apomorphine. Conceivably, a compound that attenuates PCP-stimulated behaviors while sparing apomorphine-stimulated behaviors would possess both antipsychotic efficacy and be devoid of undesirable side effects associated with dopamine blockade.