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

Andrew C. Meyer, Michael T. Bardo

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Rationale: Previous research suggests both genetic and environmental influences on substance abuse vulnerability. Objectives: The current work sought to investigate the interaction of genes and environment on the acquisition of amphetamine self-administration as well as amphetamine-stimulated dopamine (DA) release in nucleus accumbens shell using in vivo microdialysis. Methods: Inbred Lewis (LEW) and Fischer (F344) rat strains were raised in either an enriched condition (EC), social condition (SC), or isolated condition (IC). Acquisition of amphetamine self-administration (0.1 mg/kg/infusion) was determined across an incrementing daily fixed ratio (FR) schedule. In a separate cohort of rats, extracellular DA and the metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were measured in the nucleus accumbens shell following an acute amphetamine injection (1 mg/kg). Results: "Addiction-prone" LEW rats had greater acquisition of amphetamine self-administration on a FR1 schedule compared to "addiction-resistant" F344 rats when raised in the SC environment. These genetic differences were negated in both the EC and IC environments, with enrichment buffering against self-administration and isolation enhancing self-administration in both strains. On a FR5 schedule, the isolation-induced increase in amphetamine self-administration was greater in F344 than LEW rats. While no group differences were obtained in extracellular DA, gene∈×∈environment differences were obtained in extracellular levels of the metabolite DOPAC. In IC rats only, LEW rats showed attenuation in the amphetamine-induced decrease in DOPAC compared to F344 rats. IC LEW rats also had an attenuated DOPAC response to amphetamine compared to EC LEW rats. Conclusions: The current results demonstrate gene∈×∈environment interactions in amphetamine self-administration and amphetamine-induced changes in extracellular DOPAC in nucleus accumbens (NAc) shell. However, the behavioral and neurochemical differences were not related directly, indicating that mechanisms independent of DA metabolism in NAc shell likely mediate the gene∈×∈environment effects in amphetamine self-administration.

Original languageEnglish
Pages (from-to)2275-2285
Number of pages11
Issue number13
StatePublished - Jul 13 2015

Bibliographical note

Funding Information:
We thank Emily Denehy, Travis McCuddy, and Luke Holderfield for their technical assistance. This work was supported by National Institute on Drug Abuse grants DA12964 and DA05312. These experiments were completed as part of a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the University of Kentucky.

Publisher Copyright:
© 2015 Springer-Verlag Berlin Heidelberg.


  • Amphetamine
  • Dopamine
  • Environmental enrichment
  • Fischer 344
  • Gene∈×∈environment interactions
  • Inbred rat strains
  • Lewis
  • Microdialysis
  • Self-administration

ASJC Scopus subject areas

  • Pharmacology


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