title: Human Mu Opioid Receptor (OPRM1 A118G) polymorphism is associated with brain mu-opioid receptor binding potential in smokers.
abstract: Evidence points to the endogenous opioid system, and the mu-opioid receptor (MOR) in particular, in mediating the rewarding effects of drugs of abuse, including nicotine. A single nucleotide polymorphism (SNP) in the human MOR gene (OPRM1 A118G) has been shown to alter receptor protein level in preclinical models and smoking behavior in humans. To clarify the underlying mechanisms for these associations, we conducted an in vivo investigation of the effects of OPRM1 A118G genotype on MOR binding potential (BP(ND) or receptor availability). Twenty-two smokers prescreened for genotype (12 A/A, 10 */G) completed two [(11)C]carfentanil positron emission tomography (PET) imaging sessions following overnight abstinence and exposure to a nicotine-containing cigarette and a denicotinized cigarette. Independent of session, smokers homozygous for the wild-type OPRM1 A allele exhibited significantly higher levels of MOR BP(ND) than smokers carrying the G allele in bilateral amygdala, left thalamus, and left anterior cingulate cortex. Among G allele carriers, the extent of subjective reward difference (denicotinized versus nicotine cigarette) was associated significantly with MOR BP(ND) difference in right amygdala, caudate, anterior cingulate cortex, and thalamus. Future translational investigations can elucidate the role of MORs in nicotine addiction, which may lead to development of novel therapeutics.
authors.affiliation: Center for Interdisciplinary Research on Nicotine Addiction, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Riju
authors.initials: R
authors.lastname: Ray
authors.forename: Kosha
authors.initials: K
authors.lastname: Ruparel
authors.forename: Andrew
authors.initials: A
authors.lastname: Newberg
authors.forename: E Paul
authors.initials: EP
authors.lastname: Wileyto
authors.forename: James W
authors.initials: JW
authors.lastname: Loughead
authors.forename: Chaitanya
authors.initials: C
authors.lastname: Divgi
authors.forename: Julie A
authors.initials: JA
authors.lastname: Blendy
authors.forename: Jean
authors.initials: J
authors.lastname: Logan
authors.forename: Jon-Kar
authors.initials: JK
authors.lastname: Zubieta
authors.forename: Caryn
authors.initials: C
authors.lastname: Lerman
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000494:pharmacology; D011110:Polymorphism, Genetic; D049268:Positron-Emission Tomography / Q000379:methods; D017450:Receptors, Opioid, mu / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*; D014026:Nicotiana
chemical_list: C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D009538:Nicotine