title: Analysis of candidate genes for morphine preference quantitative trait locus Mop2.
abstract: Compared to DBA/2J (D2), C57BL/6J (B6) inbred mice exhibit strong morphine preference when tested using a two-bottle choice drinking paradigm. A morphine preference quantitative trait locus (QTL), Mop2, was originally mapped to proximal chromosome (Chr) 10 using a B6xD2 F2 intercross population, confirmed with reciprocal congenic strains and fine mapped with recombinant congenic strains. These efforts identified a ∼ 10-Million base pair (Mbp) interval, underlying Mop2, containing 35 genes. To further reduce the interval, mice from the D2.B6-Mop2-P1 congenic strain were backcrossed to parental D2 mice and two new recombinant strains of interest were generated: D2.B6-Mop2-P1.pD.dB and D2.B6-Mop2-P1.pD.dD. Results obtained from testing these strains in the two-bottle choice drinking paradigm suggest that the gene(s) responsible for the Mop2 QTL is one or more of 22 remaining within the newly defined interval (∼ 7.6 Mbp) which includes Oprm1 and several other genes related to opioid pharmacology. Real-time qRT-PCR analysis of Oprm1 and opioid-related genes Rgs17, Ppp1r14c, Vip, and Iyd revealed both between-strain and within-strain expression differences in comparisons of saline- and morphine-treated B6 and D2 mice. Analysis of Rgs17 protein levels also revealed both between-strain and within-strain differences in comparisons of saline- and morphine-treated B6 and D2 mice. Results suggest that the Mop2 QTL represents the combined influence of multiple genetic variants on morphine preference in these two strains. Relative contributions of each variant remain to be determined.
authors: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Electronic address: gadoyle@mail.med.upenn.edu.
authors: G A
authors: GA
authors: Doyle
authors: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors: C L
authors: CL
authors: Schwebel
authors: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors: S E
authors: SE
authors: Ruiz
authors: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors: A D
authors: AD
authors: Chou
authors: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors: A T
authors: AT
authors: Lai
authors: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors: M-J
authors: MJ
authors: Wang
authors: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Research Services, Department of Veterans Affairs Medical Center, Coatesville, PA, USA.
authors: G G
authors: GG
authors: Smith
authors: Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA.
authors: R J
authors: RJ
authors: Buono
authors: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors: W H
authors: WH
authors: Berrettini
authors: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA.
authors: T N
authors: TN
authors: Ferraro
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage; D000818:Animals; D001921:Brain / Q000502:physiology; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D004327:Drinking Behavior / Q000187:drug effects / Q000502:physiology; D058999:Drug-Seeking Behavior / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009020:Morphine / Q000008:administration & dosage*; D009294:Narcotics / Q000008:administration & dosage*; D040641:Quantitative Trait Loci; D011803:Quinine / Q000008:administration & dosage; D020710:RGS Proteins / Q000378:metabolism; D013045:Species Specificity
chemical_list: D018712:Analgesics, Non-Narcotic; D009294:Narcotics; D020710:RGS Proteins; C532880:RGS17 protein, mouse; D009020:Morphine; D011803:Quinine
keywords: IYD; Ppp1r14c; Rgs17; Vip; two-bottle choice; μ-opioid receptor