Computerized measurement of MK-801-elicited popping and hyperactivity in mice.

Abstract

MK-801, a high-affinity phencyclidine (PCP) analogue, is a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) subclass of glutamate receptor that elicits hyperactivity, stereotypic behaviors, and "popping," an explosive episodic jumping behavior, in mice. The schizophreniform psychosis precipitated by PCP in humans has stimulated interest in studying MK-801-elicited mouse behaviors for their potential development as animal models of idiopathic psychosis. We describe a computerized method for measuring popping and hyperactivity elicited by MK-801 in mice, based on vertical displacements of a platform. This computerized procedure allows for the automatic measurement of discrete "pops" per individual episode of popping behavior, the force of each one of the explosive jumps, and the duration of discrete episodes of popping; these latter measures could not be easily ascertained by visual inspection alone. Moreover, the computerized measurements facilitate quantitative evaluation of the effects of pharmacological manipulations on MK-801-elicited popping. For example, the antipsychotic haloperidol was shown to reduce significantly both MK-801-induced popping and hyperactivity. Ideally, MK-801-elicited mouse popping and hyperactivity will serve as a useful preclinical screening paradigm for potential antipsychotic medications. Additionally, it is hoped that the use of this automated system will contribute to a greater understanding of the mechanisms of MK-801-induced popping and hyperactivity.