The International Journal of Neuropsychopharmacology

Research Article

Influence of OPRM1 Asn40Asp variant (A118G) on [11C]carfentanil binding potential: preliminary findings in human subjects

Elise M. Weertsa1, Mary E. McCaula1a2, Hiroto Kuwabaraa3, Xiaoju Yanga2, Xiaoqiang Xua2, Robert F. Dannalsa3, J. James Frosta3, Dean F. Wonga1a3a4a5 and Gary S. Wanda1a2 c1

a1 Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

a2 Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

a3 Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

a4 Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

a5 Department of Environmental Health Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

Abstract

The Asn40Asp variant (A118G) of the μ opioid receptor (OPRM1) gene is thought to contribute to the development and treatment of alcohol dependence. Employing positron emission tomography (PET), we first examined whether the single nucleotide polymorphism (SNP) modifies binding potential (BPND) of the μ-selective ligand [11C]carfentanil in healthy control (Con) and 5-d abstinent alcohol-dependent (AD) subjects (unblocked basal scan). Second, we examined whether the allelic variants were associated with differences in OPRM1 occupancy by naltrexone (50 mg) in AD subjects. Con and AD carriers of the G allele (AG) had lower global BPND at the basal scan than subjects homozygous for the A allele (AA). In AD subjects, naltrexone occupancy was slightly higher in AG subjects (98.9%) compared to AA subjects (93.1%), but this was not significant. We are the first to demonstrate using PET in healthy normal and AD subjects that the A118G SNP alters OPRM1 availability.

(Received October 22 2011)

(Reviewed December 12 2011)

(Revised February 03 2012)

(Accepted February 08 2012)

(Online publication March 08 2012)

Key words

  • Alcohol use disorders;
  • genetics;
  • imaging;
  • μ opioid receptors;
  • naltrexone

Correspondence:

c1 Address for Correspondence: G. S. Wand, M.D., 720 Rutland Avenue, Ross 863, Baltimore, MD 21205, USA. Tel.: 410 955 7225 Fax: 410 955 0841 Email: gwand@jhmi.edu