Striatal dopamine d2/d3 receptor availability is reduced in methamphetamine dependence and is linked to impulsivity

Abstract

While methamphetamine addiction has been associated with both impulsivity and striatal dopamine D(2)/D(3) receptor deficits, human studies have not directly linked the latter two entities. We therefore compared methamphetamine-dependent and healthy control subjects using the Barratt Impulsiveness Scale (version 11, BIS-11) and positron emission tomography with [(18)F]fallypride to measure striatal dopamine D(2)/D(3) receptor availability. The methamphetamine-dependent subjects reported recent use of the drug 3.3 g per week, and a history of using methamphetamine, on average, for 12.5 years. They had higher scores than healthy control subjects on all BIS-11 impulsiveness subscales (p < 0.001). Volume-of-interest analysis found lower striatal D(2)/D(3) receptor availability in methamphetamine-dependent than in healthy control subjects (p < 0.01) and a negative relationship between impulsiveness and striatal D(2)/D(3) receptor availability in the caudate nucleus and nucleus accumbens that reached statistical significance in methamphetamine-dependent subjects. Combining data from both groups, voxelwise analysis indicated that impulsiveness was related to D(2)/D(3) receptor availability in left caudate nucleus and right lateral putamen/claustrum (p < 0.05, determined by threshold-free cluster enhancement). In separate group analyses, correlations involving the head and body of the caudate and the putamen of methamphetamine-dependent subjects and the lateral putamen/claustrum of control subjects were observed at a weaker threshold (p < 0.12 corrected). The findings suggest that low striatal D(2)/D(3) receptor availability may mediate impulsive temperament and thereby influence addiction.

Figure 1.

Dopamine D₂/D₃ receptor availability (BP_ND) in healthy control (white bars) and methamphetamine-dependent (black bars) subjects. Data are presented as means ± SE. Values from left and right hemispheres were averaged (weighted by number of voxels) as they were highly correlated (all p values <0.001; all correlation coefficients >0.932). *Significant group difference after correcting for age by ANCOVA, p < 0.05 (after Holm–Bonferroni correction for 3 comparisons). Smoking status was not used as a covariate because smoking status had no main effects.

Figure 2.

Regression lines illustrate the correlations for the methamphetamine (row A) and healthy control (row B) groups. The values for BIS total impulsiveness scores and BP were corrected for age and then normalized (i.e., converted to z-scores) within each group. As shown above, negative correlations in the methamphetamine group were of similar magnitude for the three striatal regions, reaching statistical significance even with Holm–Bonferroni correction in the caudate nucleus (p values = 0.002, 0.068, and 0.043 for caudate nucleus, putamen, and nucleus accumbens, respectively). The difference in correlations between methamphetamine and healthy control subjects was not significant for any region (p values = 0.086, 0.485, and 0.249 for caudate nucleus, putamen, and nucleus accumbens, respectively).

Figure 3.

Results from voxelwise regression of BP_ND on BIS total scores, shown for the combined (n = 52) (A), the healthy control (n = 30) (B), and the methamphetamine-dependent (n = 22) (C) groups. TFCE probability maps are overlaid on the averaged normalized anatomy. Statistical maps for the combined group are shown with results thresholded at TFCE-corrected p < 0.05. Data for the individual group are shown at a more liberal threshold (p < 0.2, corrected) for illustration only.