Studies on an animal model of alcoholism.

Past and ongoing studies indicate that the selectively bred P line of rats satisfies virtually all the suggested criteria for an animal model of alcoholism. They attain pharmacologically active levels of BAC and develop tolerance and physical dependence with voluntary oral ethanol ingestion, while in the free-feeding state. Ethanol is positively reinforcing to the P rats and consumption appears to be directed by the post-ingestive, pharmacological effects of ethanol, as revealed by the intragastric self-administration studies. Some interesting differences between the P and the NP lines have been uncovered. They differ in the content of serotonin in several brain regions and they respond differently to ethanol. The P rats develop acute tolerance to sedative-hypnotic doses of ethanol more rapidly than do the NP rats, and they exhibit stimulation with low doses of ethanol. These differences suggest hypotheses on mechanisms underlying alcohol-seeking behavior which can now be tested experimentally. It should be emphasized, however, that the described findings are the product of but a single genetic experiment. Clearly, replication is needed, and we are currently doing this, using a better defined, heterogeneous stock of rats. This one experiment, however, has demonstrated the feasibility of developing animal models of alcoholism and offers hope that the genetic and biological basis of alcohol-seeking behavior can be explored in the laboratory. The screening and testing of pharmacological agents able to deter alcohol-seeking behavior is an obvious practical application of this model.