Elsevier

Biochemical Pharmacology

Volume 33, Issue 8, 15 April 1984, Pages 1299-1307
Biochemical Pharmacology

Sex and strain differences in response to cocaine

https://doi.org/10.1016/0006-2952(84)90184-9Get rights and content

Abstract

After pretreatment with phenobarbital, female B6AF1 mice showed considerably higher serum glutamic oxaloacetic transaminase (SGOT) elevations and more periportal necrosis from a single injection of cocaine than males. This sex difference was androgen dependent. Castration or treatment with flutamide made males respond like females, while testosterone made females behave like males. There was no significant sex difference in enzymes of cocaine metabolism. When the mice were induced by exposure to pine bedding, males showed higher SGOT elevations and more centrilobular necrosis after cocaine than females. In this case, the sex difference could be attributed to increased levels of cytochrome P-450 and cocaine N-demethylase in liver microsomes. BALB/cBy mice on pine bedding snowed much less liver damage from cocaine than B6AF1 mice, but they were more sensitive to norcocaine and N-hydroxy norcocaine. This difference was correlated with low levels of cocaine N-demethylase in the BALB/cBy mice. Liver microsomes from phenobarbital-induced BALB/cBy mice had less norcocaine N-hydroxylase activity than those from B6AF1 mice. These studies demonstrate that the pattern of sex and strain differences in liver damage from cocaine depends on the inducing agent and can be related to a large extent to the microsomal enzymes induced by that agent.

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