Quantitative trait locus analysis identifies rat genomic regions related to amphetamine-induced locomotion and Galpha(i3) levels in nucleus accumbens.
Identification of the genetic factors that underlie stimulant responsiveness in animal models has significant implications for better understanding and treating stimulant addiction in humans. F(2) 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 Galpha(i3). A 'suggestive' QTL (LRS(max)=12.5) was observed for AIL in a region of chromosome 2 that overlaps with the Galpha(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.
Potenza
Marc N
MN
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, USA. marc.potenza@yale.edu
Brodkin
Edward S
ES
Yang
Bao-Zhu
BZ
Birnbaum
Shari G
SG
Nestler
Eric J
EJ
Gelernter
Joel
J
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D023281:Genomics / Q000379:methods*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics*; D009714:Nucleus Accumbens / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D040641:Quantitative Trait Loci / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew
D000661:Amphetamine; C498819:GNAI3 protein, human; D019206:GTP-Binding Protein alpha Subunits, Gi-Go