Abstract

The systematic comparison between Fischer and Lewis rats is a popular animal model of genetic factors in drug abuse. Although genetic and environmental factors interact to affect drug abuse in humans, analogous effects have not yet been reported within the Fischer-Lewis model. In order to assess the contributions and interaction of genotype and early maternal environment on responses to a drug of abuse, the present study employed a cross-fostering design, where male and female Fischer and Lewis pups were reared by unrelated dams of their own strain (in-fostered) or of the other strain (cross-fostered). As adults, rats from both strains were tested for their ability to acquire a conditioned taste aversion to a novel saccharin solution that had been repeatedly paired with an injection of cocaine (32 mg/kg, subcutaneous). In-fostered Fischer females acquired significantly weaker aversions than in-fostered Lewis females across the multiple saccharin-cocaine pairings. However, cross-fostered Fischer females exhibited aversions that were not only significantly stronger than their in-fostered Fischer counterparts, but identical to all groups of the Lewis genotype. No strain differences or cross-fostering effects were observed in the males. The data with the female subjects cannot be accounted for simply by the genetic strain of the subjects and demonstrate a clear gene-environment interaction effect on responses to the aversive effects of cocaine in Fischer and Lewis rats. Implications for studying maternal behavior as a source of epigenetic modulation of drug abuse vulnerability were discussed.

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