The effect of olanzapine pretreatment on acute cocaine toxicity in mice

Abstract

Background. Acute cocaine poisoning causes neuroexcitation and can be fatal. The toxic effects of cocaine can be attenuated by antagonists of serotonin, muscarinic cholinergic, and dopamine receptors. Olanzapine, an atypical antipsychotic medication, is an antagonist of these receptors. The objective of this study is to evaluate the efficacy of olanzapine pretreatment for attenuation of acute cocaine toxicity using a mouse model. Methods. Eighty male CF-1 mice were randomly assigned to olanzapine (1 mg/kg) or placebo pretreatment. Fifteen minutes later, all animals received 103 mg/kg intraperitoneal cocaine. Results. Overall mortality was 11% for olanzapine-treated animals and 45% for placebo. Olanzapine also appeared to alter the characteristics of seizures due to cocaine. Conclusions. In this model of acute cocaine toxicity, olanzapine pretreatment attenuated acute cocaine toxicity. Olanzapine should be evaluated further as a potential treatment for acute cocaine poisoning.

Key words:

• Cocaine
• Antipsychotic
• Overdose

Acknowledgments

This work was supported by NIH-DA-020573 to Dr. Heard and by the University of Colorado Department of Surgery. Dr. Heard conceived the study, performed the experiments, and wrote the first draft of the manuscript. Drs. Krier and Cleveland refined the experimental procedures, performed the experiments, and reviewed and contributed to the final manuscript.