1. ¹Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
2. ²Department of Psychiatry, VA CT Healthcare Center, West Haven, CT, USA
3. ³Department of Psychiatry and Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
4. ⁴Departments of Psychiatry and Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX, USA
5. ⁵Department of Genetics, Yale University School of Medicine, New Haven, CT, USA
6. ⁶Department of Neurobiology, Yale University School of Medicine, New Haven, CT, USA

Correspondence: Dr MN Potenza, Yale University School of Medicine, Connecticut Mental Health Center, Room S-104, 34 Park Street, New Haven, CT 06519, USA. Tel: 1 203 974 7356; Fax: +1 203 974 7366; E-mail: marc.potenza@yale.edu

Received 25 May 2007; Revised 11 December 2007; Accepted 11 December 2007; Published online 23 January 2008.

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 (LRS_max)=21.3) for AIL and on chromosome 2 (LRS_max=22.0) for G_i3. A 'suggestive' QTL (LRS_max=12.5) was observed for AIL in a region of chromosome 2 that overlaps with the G_i3 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.