Characterization of MK-801-induced behavior as a putative rat model of psychosis

The objective of this study was to characterize the behavior induced by the N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine maleate) in r ats as a model of psychosis. The temporal profile, dose dependence, age, an d sex differences of the behavior are described. A gas chromatographic meth od for the analysis of MK-801 in plasma and brain was developed. Female rat s showed 4 to 10 times more MK-801-induced behavior and displayed around 25 times higher serum and brain concentrations of MK-801 than male rats. Twen ty-one neuroactive compounds, including a number of excitatory amino acid-a ctive substances, were tested for the effect on MK-801-induced behavior. Ne uroleptics blocked MK-801-induced behavior in a dose-dependent manner that correlated to their antipsychotic potency in humans. Adenosine receptor ago nists and an,N-methyl-D-aspartate receptor-associated glycine site antagoni st showed putative antipsychotic effects. In conclusion, MK-801-imduced beh avior represents a rat excitatory amino acid hypofunction model of psychosi s that appears to be of clinical relevance and may be of value in the searc h for new antipsychotic agents.