The Behavioral and Molecular Consequences of Concurrent Cocaine and Ethanol Use
Zipperly, Morgan Elizabeth
Knackstedt, Lori A
Korey, Christopher A
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Concurrent cocaine and ethanol use is more common than any other drug combination, and such polydrug use often results in increased consumption of both substances. We developed an animal model of cocaine and alcohol co-abuse in which rat self-administered intravenous cocaine for 2 hours followed by oral alcohol for 6 hours. We hypothesized that subjects permitted access to both drugs would consume more ethanol and cocaine compared to groups permitted access to only one drug. We also predicted that self-administration of both drugs would reduce protein expression of mGluR5, GLT-1, and xCT and elevate levels of Homer protein expression. Cocaine and ethanol consumption were measured over a 12-day self-administration period. Immediately following the self-administration period, subjects completed 2 weeks of extinction training, followed by reinstatement. We measured Homer, mGluR5, GLT-1, and xCT protein concentrations via microdialysis during reinstatement. No significant difference in substance consumption was found between drug-consuming groups. There was a significant interaction between cocaine and ethanol on Homer protein expression. No other significant effects were found, although mGluR5 and GLT-1 levels were decreased for all drug-consuming groups. These results indicate that there are molecular and behavioral interactions between cocaine and ethanol when consumed concomitantly. The fact that cocaine and alcohol-consuming subjects chose to consume both substances indicates that this polydrug use results in a pleasurable experience, possibly reducing the negative side-effects of both substances.