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NIDA. (2015, May 29). Interactions of environmental conditions and genetic risk for drug taking. Retrieved from

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Science Highlight

May 29, 2015

Amphetamine self-administration and dopamine function: assessment of gene × environment interactions in Lewis and Fischer 344 rats

DNA molecule

Both genetic and environmental factors contribute to the development of substance use disorders. These factors can interact in ways that confer additional risk based on the combination of genotype and environment. Such gene-by-environment interactions can be explored by studying rats that have been specifically bred to be genetically susceptible or resistant to drug use. For example, the inbred rat strain LEW has been shown to self-administer stimulant drugs more readily than the F344 strain. With environmental factors held constant, differences between the strains are due to genetic factors, while differences within a single strain may be attributable to environmental factors.

This study examined gene-by-environment interactions in susceptibility to drug use by raising LEW and F344 rats in varied environmental conditions. Some were housed in the standard, social condition (SC) of multiple rats in one cage, others were housed in enriched conditions (EC), which involved group housing and exposure to novel objects, and others were housed in isolated conditions (IC), which removed all social and object stimuli. The enriched rats of both strains showed less amphetamine self-administration, while the isolated rats of both strains were more prone to self-administration of amphetamine, with the IC condition causing even greater self-administration in the F344 strain than the LEW strain. The SC rats differed according to genotype, with SC LEW rats taking more amphetamine than SC F344 rats. An interaction of strain and environment could also be seen at a neurochemical level: while no significant differences in amphetamine-stimulated extracellular DA were observed between strains or rearing environments, levels of the dopamine metabolite DOPAC were decreased less in LEW rats raised in isolation in response to amphetamine than in F344 rats raised in isolation, an effect that was not seen in rats raised in either the social or enriched environment. These results highlight how genetic differences can cause altered responses to environmental factors. The overall protective effects of the EC indicate that environmental enrichment can protect against some genetic risk for drug use.


Meyer AC, Bardo MT. Amphetamine self-administration and dopamine function: assessment of gene × environment interactions in Lewis and Fischer 344 rats. Psychopharmacology (Berl). 2015 Jan 9. [Epub ahead of print] PubMed PMID:[25566972].