Effects of Cross‐Fostering on Alcohol Preference and Correlated Responses to Selection in High‐ and Low‐Alcohol‐Preferring Mice

Abstract

Selectively bred rodent lines are valuable tools for investigating gene×environment interactions related to risk for alcoholism in humans. Early maternal environment is one particular factor known for critically influencing neural, hormonal, and behavioral outcomes in adulthood. Cross-fostering is a procedure that may be used to explore the role of genotype-dependent maternal influences on phenotypic variability in adulthood. The purpose of these experiments was to examine the effects of cross-fostering on free-choice alcohol drinking and correlated responses to selection for alcohol preference in mice selectively bred for high (HAP2) and low (LAP2) alcohol preference. Mice were assigned to one of the following treatments: SHAM (pups that were fostered to their original biological mother), IN (pups that were fostered to a different mother of the same line), and CROSS (pups that were fostered to a mother of a different line). Mice were tested in adulthood for (i) free 24-hour access to alcohol for a period of 28days; (ii) the expression of the acoustic startle response and fear-potentiated startle (FPS); and (iii) handling-induced convulsions (HICs) during acute alcohol withdrawal. Overall, the expression of the alcohol preference selection phenotype was robust in all groups (HAP2>LAP2). Cross-fostering produced a moderate but significant reduction in g/kg alcohol drinking and preference scores in HAP2 mice (CROSS<SHAM) but had no effect in LAP2 mice. Cross-fostering did not affect the expression of correlated responses to selection: acoustic startle response (HAP2>LAP2), FPS (HAP2>LAP2), HICs (LAP2>HAP2). It appears that maternal environment can modify the expression of the high-alcohol-preference phenotype in HAP2 selectively bred mice. These results suggest a gene×environment interaction with respect to the expression of the high-alcohol-preference selection phenotype but not correlated responses to selection.