Characterization of MK-801-induced behavior as a putative rat model of psychosis.
Peter Andiné, Nina Widermark, R. Axelsson, G. Nyberg, Ulla Olofsson, E. Mårtensson, Mats Sandberg
Journal of Pharmacology and Experimental Therapeutics September 1, 1999 DOI: 10.1016/s0022-3565(24)35047-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | MK-801 (dizocilpine maleate) |
| Key findings | MK-801-induced behavior in rats is sex-dependent, with females showing 4-10 times more behavior and about 25 times higher drug concentrations. Neuroleptics blocked this behavior dose-dependently, correlating with human antipsychotic potency, suggesting the model's clinical relevance. |
Abstract
The objective of this study was to characterize the behavior induced by the N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine maleate) in rats as a model of psychosis. The temporal profile, dose dependence, age, and sex differences of the behavior are described. A gas chromatographic method for the analysis of MK-801 in plasma and brain was developed. Female rats 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. Twenty-one neuroactive compounds, including a number of excitatory amino acid-active substances, were tested for the effect on MK-801-induced behavior. Neuroleptics blocked MK-801-induced behavior in a dose-dependent manner that correlated to their antipsychotic potency in humans. Adenosine receptor agonists and an N-methyl-D-aspartate receptor-associated glycine site antagonist showed putative antipsychotic effects. In conclusion, MK-801-induced behavior represents a rat excitatory amino acid hypofunction model of psychosis that appears to be of clinical relevance and may be of value in the search for new antipsychotic agents.