Individual differences in drug dependence in rats: The role of genetic factors and life events

This present review discusses the results from an animal model in which these three different hit are currently being investigated. The apomorphine susceptible (APO-SUS) and apomorphine unsusceptible (APO-UNSUS) rats, originally selected on the basis of their behavioural response to the dopaminergic agonist apomorphine, were recently found to be genetically different in the number of gene copies of a component of the γ-secretase complex called Aph-1b. Whereas APO-UNSUS rats have three copies of the gene, APO-SUS rats have either 1 or 2 copies. In addition we have shown that these rats show differences in cocaine and alcohol self-administration, and that both early life events and late environmental factors can alter this self-administration behaviour. Thus, the data so far support the hypothesis that the APO-SUS and APO-UNSUS rats offer an interesting animal model for drug dependence in which genes and environment interact. We finally propose a theoretical model which can explain this gene-environment interaction.