Abstract
BackgroundAccumulating epidemiological evidence points to the role of genetic background as a modulator of the capacity of adverse early experiences to give rise to mental illness. However, direct evidence of such gene-environment interaction in the context of substance abuse is scarce. In the present study we investigated whether the impact of early life experiences on cocaine intake in adulthood depends on genetic background. In addition, we studied other behavioral dimensions associated with drug abuse, i.e. anxiety- and depression-related behaviors.Methodology/Principal FindingsFor this purpose, we manipulated the maternal environment of two inbred mouse strains, the C57BL/6J and DBA/2J by fostering them with non-related mothers, i.e. the C3H/HeN and AKR strains. These mother strains show respectively high and low pup-oriented behavior. As adults, C57BL/6J and DBA/2J were tested either for cocaine intravenous self-administration or in the elevated plus-maze and forced swim test (FST). We found that the impact of maternal environment on cocaine use and a depression-related behavior depends upon genotype, as cocaine self-administration and behavior in the FST were influenced by maternal environment in DBA/2J, but not in C57BL/6J mice. Anxiety was not influenced by maternal environment in either strain.Conclusions/SignificanceOur experimental approach could contribute to the identification of the psychobiological factors determining the susceptibility or the resilience of certain individuals to develop psychopathologies.
Highlights
Clinical and epidemiological studies point to an important role of adverse early experiences in the vulnerability to a variety of psychiatric disorders in adulthood
We show that the impact of early life experiences on cocaine use in adulthood is dependent on the genotype, as we found the DBA strain sensitive and the C57 strain resistant to the influence of maternal environment on cocaine intake in adulthood
Adult mice, exposed as pups to distinct maternal environments, were examined in cocaine SA and measures for depression- and anxiety- related behaviors, two behavioral dimensions that are frequently associated with human drug abuse [26]
Summary
Clinical and epidemiological studies point to an important role of adverse early experiences in the vulnerability to a variety of psychiatric disorders in adulthood. Environment in particular would affect the long-term neurobiological and psychosocial development of the offspring and modulate the vulnerability to mood-, anxiety-, psychosis- or drug use-related disorders [1,2,3,4,5,6]. Their influence may be strong and pervasive, early experiences rarely determine the nature and outcome of the psychopathology [7,8]. Accumulating epidemiological evidence points to the role of genetic background as a modulator of the capacity of adverse early experiences to give rise to mental illness. We studied other behavioral dimensions associated with drug abuse, i.e. anxiety- and depression-related behaviors
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