Abstract
ObjectiveTo determine if overnight tobacco abstinent carriers of the AG or GG (*G) vs. the AA variant of the human mu opioid receptor (OPRM1) A118G polymorphism (rs1799971) differ in [11C]carfentanil binding after tobacco smoking.MethodsTwenty healthy American male smokers who abstained from tobacco overnight were genotyped and completed positron emission tomography (PET) scans with the mu opioid receptor agonist, [11C]carfentanil. They smoked deniconized (denic) and average nicotine (avnic) cigarettes during the PET scans.ResultsSmoking avnic cigarette decreased the binding potential (BPND) of [11C]carfentanil in the right medial prefrontal cortex (mPfc; 6,56,18), left anterior medial prefrontal cortex (amPfc; −2,46,44), right ventral striatum (vStr; 16, 3, −10), left insula (Ins; −42,10, −12), right hippocampus (Hippo; 18, −6, −14) and left cerebellum (Cbl; −10, −88, −34), and increased the BPND in left amygdala (Amy; −20,0, −22), left putamen (Put; −22, 10, −6) and left nucleus accumbens (NAcc; −10,12, −8). In the AA allele carriers, avnic cigarette smoking significantly changed the BPND compared to after denic smoking in most brain areas listed above. However in the *G carriers the significant BPND changes were confirmed in only amPfc and vStr. Free mu opioid receptor availability was significantly less in the *G than the AA carriers in the Amy and NAcc.ConclusionThe present study demonstrates BPND changes induced by avnic smoking in OPRM1 *G carriers were blunted compared to the AA carriers. Also *G smokers had less free mu opioid receptor availability in Amy and NAcc.
Highlights
Many studies with mice have demonstrated that nicotine induces endogenous brain opioid release (Davenport et al, 1990; Dhatt et al, 1995; Isola et al, 2009)
The present study demonstrates BPND changes induced by avnic smoking in OPRM1 *G carriers were blunted compared to the AA carriers
The present study reports the role of OPRM1 A118G in brain endogenous opioid release following tobacco smoking as measured by [11C]carfentanil displacement with denic and 1.0 mg nicotine avnic cigarettes
Summary
Many studies with mice have demonstrated that nicotine induces endogenous brain opioid release (Davenport et al, 1990; Dhatt et al, 1995; Isola et al, 2009). C57BL/6 mice treated with large doses of nicotine results in marked tolerance to nicotine antinociception (Galeote et al, 2006). The C57B4/6 mu opioid knockout mice develop tolerance to nicotine antinociception more quickly. The antinociceptive actions of nicotine in rodents are not reduced by mu opioid antagonists. Nicotine/tobacco smoking is not an effective analgesic. Some brain evoked potentials due to painful laser stimuli are reduced, but C fiber effects are enhanced by tobacco smoking (Miyazaki et al, 2009; Miyazaki et al, 2010)
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