Quantitative trait locus analysis identifies rat genomic regions related to amphetamine-induced locomotion and Gαi3 levels in nucleus accumbens

Marc N. Potenza, Edward S. Brodkin, Bao Zhu Yang, Shari G. Birnbaum, Eric J. Nestler, Joel Gelernter

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Identification of the genetic factors that underlie stimulant responsiveness in animal models has significant implications for better understanding and treating stimulant addiction in humans. F2 progeny derived from parental rat strains F344/NHsd and LEW/NHsd, which differ in responses to drugs of abuse, were used in quantitative trait locus (QTL) analyses to identify genomic regions associated with amphetamine-induced locomotion (AIL) and G-protein levels in the nucleus accumbens (NAc). The most robust QTLs were observed on chromosome 3 (maximal log ratio statistic score (LRSmax)=21.3) for AIL and on chromosome 2 (LRSmax=22.0) for Gαi3. A 'suggestive' QTL (LRSmax=12.5) was observed for AIL in a region of chromosome 2 that overlaps with the Gαi3 QTL. Novelty-induced locomotion (NIL) showed different QTL patterns from AIL, with the most robust QTL on chromosome 13 (LRS max=12.2). Specific unique and overlapping genomic regions influence AIL, NIL, and inhibitory G-protein levels in the NAc. These findings suggest that common genetic mechanisms influence certain biochemical and behavioral aspects of stimulant responsiveness.

Original languageEnglish (US)
Pages (from-to)2735-2746
Number of pages12
JournalNeuropsychopharmacology
Volume33
Issue number11
DOIs
StatePublished - Oct 2008

Keywords

  • Addiction genetics
  • Amphetamine
  • G proteins
  • Novelty-induced locomotion
  • Nucleus accumbens
  • QTL

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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