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Alcohol makes rats more vulnerable to compulsive cocaine use

Prior alcohol use enhances vulnerability to compulsive cocaine self-administration by promoting degradation of HDAC4 and HDAC5

American Association for the Advancement of Science

Alcohol Makes Rats More Vulnerable to Compulsive Cocaine Use: Rats given alcohol for 10 days prior to cocaine exhibited enhanced cocaine-addiction behavior, including continuing to seek cocaine despite receiving a brief electric shock when they did so, a new study reports. Results suggest alcohol increases compulsive cocaine use by promoting the breakdown of important proteins in the nucleus accumbens, a brain region critical for reward-based memory. While addiction to cocaine is commonly preceded by use of other substances such as alcohol, nicotine and marijuana, the biological mechanisms by which these "gateway drugs" contribute to cocaine addiction are only beginning to be understood. Since only a fraction (about 21%) of cocaine users progress to compulsive use, it is thought that both genetic and environmental factors are involved in vulnerability to cocaine addiction. Edmund Griffin Jr. and colleagues evaluated cocaine-seeking behaviors of rats that had been given alcohol for 10 days prior to cocaine administration compared to rats without prior alcohol exposure, as well as rats given alcohol and cocaine concurrently. The rats with longer-term prior alcohol exposure were more persistent in seeking cocaine. For example, those rats pressed a lever to release cocaine an average of 58 times during a period of the experiment when no drugs were released; rats without alcohol exposure pressed the lever 18 times. Conversely, prior cocaine use had no effect on rats' alcohol preference. The researchers also found that alcohol promoted the degradation of two proteins - histone deacetylases 4 and 5 - in the rats' brains. Breakdown of these proteins creates a permissive environment for cocaine-induced gene expression, they report. This finding also indicates that both alcohol and nicotine act through similar molecular mechanisms to increase vulnerability to cocaine.

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