Cross-fostering and the extinction of cocaine's conditioned aversive effects: Evidence for gene-environment interaction

Although genetic and early environmental factors interact to affect drug abuse in humans, surprisingly few tractable laboratory animal models have been developed. Using reciprocal cross-fostering of the inbred Fischer and Lewis rat strains, we recently reported significant gene-environment interaction effects on responses to the aversive properties of 32 mg/kg subcutaneous cocaine, but only in females [Roma PG., Davis CM, Riley AL. Effects of cross-fostering on cocaine-induced conditioned taste aversions in Fischer and Lewis rats. Dev Psychobiol 2007;49:172-9]. The present study describes a follow-up analysis tracking the extinction of the equally acquired cocaine aversions in the adult male Fischer and Lewis rats raised by either Fischer or Lewis dams (n = 11-12/group). Based on mean consumption, after eight saccharin-saline pairings, the in-fostered Fischer rats never extinguished while the Lewis animals fully extinguished; however, the cross-fostered Fischer rats partially extinguished, while extinction was completely suppressed in the cross-fostered Lewis animals. Based on documented strain differences in avoidance behavior and stress reactivity, the data were interpreted in terms of differential sensitivity to conditioned aversive stimulation. These data join other examples of cross-fostering effects on physiology and behavior in these strains and further support the use of the Fischer-Lewis model for exploring gene-environment interaction in drug-induced phenotypes.