@article{ed846820e69248d0b849e4641b3fc2cc,
title = "Quantitative trait locus analysis identifies rat genomic regions related to amphetamine-induced locomotion and Gαi3 levels in nucleus accumbens",
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.",
keywords = "Addiction genetics, Amphetamine, G proteins, Novelty-induced locomotion, Nucleus accumbens, QTL",
author = "Potenza, \{Marc N.\} and Brodkin, \{Edward S.\} and Yang, \{Bao Zhu\} and Birnbaum, \{Shari G.\} and Nestler, \{Eric J.\} and Joel Gelernter",
note = "Funding Information: This work was supported by a Young Investigator Award from the National Alliance for Research in Schizophrenia and Depression (NARSAD), a Drug Abuse Research Scholar Program in Psychiatry Award from the American Psychiatric Association and the National Institute on Drug Abuse (K12-DA00366), the Clinician Scientist Training Program (K12-DA00167), the US Department of Veterans Affairs (the VA Connecticut–Massachusetts Mental Illness Research, Education and Clinical Center (MIRECC), VA Research Enhancement Award program (REAP) and the Veterans Affairs Neuroscience and Traumatic Brain Injuries Postdoctoral Fellowship), NIDA R01 DA12849, NIAAA R01 AA11330, NIDA P01 DA08227, NIMH P50 MH66172, Burroughs Wellcome Fund Career Award in the Biomedical Sciences, and NIMH KO8-MH068586. We thank Xingguang Luo, Eric Londin, Michael Bernabeo, Yong Huang, and Anne Marie Lacobelle for technical assistance and Elaine F Remmers and Ronald L Wilder for advice on QTL methodologies. Funding Information: The authors report that they have no conflicts of interest over the past 3 years to report as related to the subject of the report. Dr Potenza has received financial support or compensation for the following: Dr Potenza consults for and is an advisor to Boehringer Ingelheim; has consulted for and has financial interests in Somaxon; has received research support from the National Institutes of Health, Veteran{\textquoteright}s Administration, Mohegan Sun, and Forest Laboratories, Ortho-McNeil and Oy-Control/Biotie Pharmaceuticals; has participated in surveys, mailings, or telephone consultations related to drug addiction, impulse control disorders, or other health topics; has consulted for law offices and the federal public defender{\textquoteright}s office in issues related to impulse control disorders; has performed grant reviews for the National Institutes of Health and other agencies; has given academic lectures in grand rounds, CME events, and other clinical or scientific venues; has generated books or book chapters for publishers of mental health texts; and provides clinical care in the Connecticut Department of Mental Health and Addiction Services Problem Gambling Services Program. Dr Brodkin has received financial support or compensation for the following: Dr Brodkin has performed grant reviews for the US Civilian Research and Development Foundation, the New Jersey Governor{\textquoteright}s Council on Autism, and the US Department of Defense Autism Spectrum Disorder Research Program (grant review organized by Constella Group Inc.); is a member of the Gerson Lehrman Group Healthcare Council (although not provided any services or received any compensation from Gerson Lehrman Group to date); has received research support from the National Institutes of Health, the Burroughs Wellcome Fund, the Cure Autism Now Foundation, NARSAD, the Philadelphia Foundation, and the Department of Veteran Affairs; and has given academic lectures in grand rounds and other clinical or scientific venues. Dr Gelernter has received financial support or compensation for the following: related to consultation for Columbia University, the Thailand Center for Excellence for Life Sciences (TCELS), the University of CT Health Center, NIH, and Faegre \& Benson; related to grant reviews for the National Institutes of Health; and related to academic lectures and editorial functions in various scientific venues (including the ACNP). Drs Yang, Birnbaum, and Nestler do not have any additional financial support, compensation, or personal financial holdings to disclose according to journal policy.",
year = "2008",
month = oct,
doi = "10.1038/sj.npp.1301667",
language = "English",
volume = "33",
pages = "2735--2746",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Springer Nature",
number = "11",
}