title: Amphetamine self-administration and dopamine function: assessment of gene × environment interactions in Lewis and Fischer 344 rats.
abstract: BACKGROUND
  Previous research suggests both genetic and environmental influences on substance abuse vulnerability.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Psychiatry, University of Vermont, UHC-SATC Room 1415, 1 So. Prospect Street, Burlington, VT, 05401, USA. acmeyer@uvm.edu.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Meyer
authors.affiliation: Department of Psychology, University of Kentucky, Lexington, KY, USA.|Center for Drug Abuse Research Translation, Lexington, KY, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Bardo
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism*; D000661:Amphetamine / Q000008:administration & dosage*; D000818:Animals; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D059647:Gene-Environment Interaction; D008297:Male; D017551:Microdialysis / Q000379:methods; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D012646:Self Administration; D013045:Species Specificity
chemical_list: D015102:3,4-Dihydroxyphenylacetic Acid; D000661:Amphetamine; D004298:Dopamine
keywords: Amphetamine; Dopamine; Environmental enrichment; Fischer 344; Gene × environment interactions; Inbred rat strains; Lewis; Microdialysis; Self-administration