Nicotine-specific and non-specific effects of cigarette smoking on endogenous opioid mechanisms.
This study investigates differences in μ-opioid receptor mediated neurotransmission in healthy controls and overnight-abstinent smokers, and potential effects of the OPRM1 A118G genotype. It also examines the effects of smoking denicotinized (DN) and average nicotine (N) cigarettes on the μ-opioid system. Positron emission tomography with (11)C-carfentanil was used to determine regional brain μ-opioid receptor (MOR) availability (non-displaceable binding potential, BPND) in a sample of 19 male smokers and 22 nonsmoking control subjects. Nonsmokers showed greater MOR BPND than overnight abstinent smokers in the basal ganglia and thalamus. BPND in the basal ganglia was negatively correlated with baseline craving levels and Fagerström scores. Interactions between group and genotype were seen in the nucleus accumbens bilaterally and the amygdala, with G-allele carriers demonstrating lower BPND in these regions, but only among smokers. After smoking the DN cigarette, smokers showed evidence of MOR activation in the thalamus and nucleus accumbens. No additional activation was observed after the N cigarette, with a mean effect of increases in MOR BPND (i.e., deactivation) with respect to the DN cigarette effects in the thalamus and left amygdala. Changes in MOR BPND were related to both Fagerström scores and changes in craving. This study showed that overnight-abstinent smokers have lower concentrations of available MORs than controls, an effect that was related to both craving and the severity of addiction. It also suggests that nicotine non-specific elements of the smoking experience have an important role in regulating MOR-mediated neurotransmission, and in turn modulating withdrawal-induced craving ratings.
Neuroscience Graduate Program, University of Michigan, 500 S State St., Ann Arbor, MI 48109, USA; Molecular and Behavioral Neuroscience Institute, University of Michigan, 500 S State St., Ann Arbor, MI 48109, USA. Electronic address: emilybn@umich.edu.
Emily B
EB
Nuechterlein
Molecular and Behavioral Neuroscience Institute, University of Michigan, 500 S State St., Ann Arbor, MI 48109, USA; Department of Pharmacology, University of Michigan, 500 S State St., Ann Arbor, MI 48109, USA.
Lisong
L
Ni
Department of Pharmacology, University of Michigan, 500 S State St., Ann Arbor, MI 48109, USA.
Edward F
EF
Domino
Molecular and Behavioral Neuroscience Institute, University of Michigan, 500 S State St., Ann Arbor, MI 48109, USA; Department of Radiology, University of Michigan, 500 S State St., Ann Arbor, MI 48109, USA; Department of Psychiatry, University of Michigan, 500 S State St., Ann Arbor, MI 48109, USA.
Jon-Kar
JK
Zubieta
D000328:Adult; D000701:Analgesics, Opioid; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D066249:Craving / Q000187:drug effects / Q000502:physiology; D005283:Fentanyl / Q000031:analogs & derivatives; D060005:Genotyping Techniques; D006801:Humans; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D018847:Opioid Peptides / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index; D012907:Smoking / Q000235:genetics / Q000378:metabolism* / Q000523:psychology; D055815:Young Adult
D000701:Analgesics, Opioid; D002250:Carbon Radioisotopes; D018722:Nicotinic Agonists; C485764:OPRM1 protein, human; D018847:Opioid Peptides; D019275:Radiopharmaceuticals; D017450:Receptors, Opioid, mu; D009538:Nicotine; C017114:carfentanil; D005283:Fentanyl
A118G; OPRM1; PET; Smoking; [11C]-Carfentanil