dizocilpine-maleate and acivicin

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.

Topics: Aging; Animals; Brain; Disease Models, Animal; Dizocilpine Maleate; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Female; GABA Antagonists; Isoxazoles; Male; Motor Activity; Psychoses, Substance-Induced; Rats; Rats, Sprague-Dawley; Receptors, GABA; Sex Characteristics; Stereotyped Behavior; Stereotypic Movement Disorder