Mu Opioid Receptor Binding Correlates with Nicotine Dependence and Reward in Smokers.

The rewarding effects of nicotine are associated with activation of nicotine receptors. However, there is increasing evidence that the endogenous opioid system is involved in nicotine's rewarding effects. We employed PET imaging with [11C]carfentanil to test the hypotheses that acute cigarette smoking increases release of endogenous opioids in the human brain and that smokers have an upregulation of mu opioid receptors (MORs) when compared to nonsmokers. We found no significant changes in binding potential (BPND) of [11C]carfentanil between the placebo and the active cigarette sessions, nor did we observe differences in MOR binding between smokers and nonsmokers. Interestingly, we showed that in smokers MOR availability in bilateral superior temporal cortices during the placebo condition was negatively correlated with scores on the Fagerström Test for Nicotine Dependence (FTND). Also in smokers, smoking-induced decreases in [11C]carfentanil binding in frontal cortical regions were associated with self-reports of cigarette liking and wanting. Although we did not show differences between smokers and nonsmokers, the negative correlation with FTND corroborates the role of MORs in superior temporal cortices in nicotine addiction and provides preliminary evidence of a role of endogenous opioid signaling in frontal cortex in nicotine reward

Line plots of mean concentrations across subjects of nicotine in plasma versus time of active and placebo cigarette scans.

<p>PET data acquisition began between 5 and 10 min on the time axis in individual subjects.</p

Concentrations of nicotine and metabolites in plasma during active and placebo cigarette scans.

<p>Mean ± standard deviation (ng/mL) of individual subjects' means across 2–75 min, except for the second nicotine row representing nicotine concentrations only from 2–10 min.</p><p>Limits of quantification were 1 ng/mL for cotinine, OH-cotinine and norcotinine, and 2.5 ng/mL for nicotine at individual time point.</p><p>* Active cigarette scan values > placebo cigarette scan value at p<0.01; paired t-test.</p>#<p>Smoker > nonsmoker at p<0.00001; t-test.</p><p>Concentrations of nicotine and metabolites in plasma during active and placebo cigarette scans.</p

Positive correlation clusters of Δ[¹¹C]carfentanil binding potential (BP_ND) (placebo - active) versus ΔVAS of feel the effect category in smokers, displayed on trans-axial images of a gray-matter probability maps.

<p>Scatter plots of cluster Δ[¹¹C]carfentanil BP_ND values to ΔVAS are shown together with regression lines. VAS stands for the visual analog scale of smoking effects, and <i>R²</i> stands for the coefficient of determination of linear regression.</p

Correlation clusters of [¹¹C]carfentanil binding potential (BP_ND) of placebo-cigarette scans versus the Fagerström Test for Nicotine Dependence (FTND) in smokers, displayed on trans-axial images of a gray-matter probability maps.

<p>Right panels show scatter plots using cluster [¹¹C]carfentanil BP_ND, together with regression line. In regression equations, <i>R²</i> stands for the coefficient of determination.</p