Article Figures & Data
Figures
- Figure 1.
Diagram of the experimental design. Subjects were tested on two separate days. On each day, they were scanned first with [11C]raclopride, and this was followed by an FDG scan. On one of the days, the subjects received intravenous placebo (saline solution); and on the other day, they received intravenous MP, which was given 5 min before [11C]raclopride injection.
- Figure 2.
Behavioral (A) and cardiovascular (B) effects of MP in controls (black symbols) and alcoholics (gray symbols). A, Self-reports of drug effects, high, and stimulated were significantly larger in controls than in alcoholics (p < 0.05). Cardiovascular effects did not differ between groups.
- Figure 3.
SPM results for the comparison of MP versus placebo on the BPND images from [11C]raclopride in the controls and in the alcoholic subjects (pu < 0.005). The regions shown are those where MP decreased BPND, which correspond to the regions where MP increased DA. The contrast controls > alcoholics indicates that MP induced greater decreases in BPND (reflecting greater DA increases) in the controls than in the alcoholics. There were no regions where alcoholics showed greater BPND decreases than the controls. The color scale indicates the t values for the comparisons.
- Figure 4.
SPM results for the comparison of MP versus placebo on the relative metabolic images in the controls and in the alcoholic subjects (pu < 0.005). The contrast shows the regions where MP increased metabolism (yellow/red) and where it decreased metabolism (blue). The contrast alcoholic > controls indicates the regions where MP induced greater decreases in metabolism (blue) and greater increases in metabolism (red) in alcoholics than in the controls. The color scale indicates the t values for the comparisons.
- Figure 5.
SPM results for the voxelwise analysis where the correlations (positive) between MP-induced changes in BPND (reflecting DA increases) and regional brain metabolism (reflecting changes in brain activity) were significant for the controls and the alcoholic (pu > 0.001). Decreases in BPND reflect DA increases, such that positive correlations indicate that DA increases are associated with decreases in metabolism. There are more extensive cortical correlations in the alcoholics than in the controls. The color scale indicates the t values for the comparisons.
- Figure 6.
Regression plots for the controls and the alcoholics for the correlation between MP-induced changes in BPND and changes in relative metabolism. The negative values for ΔBPND reflect lower BPND measures with MP (i.e., DA increases with MP), and negative ΔFDG reflect lower values with MP (decreased metabolism with MP). Open symbols and dashed lines represent controls; and closed symbols and continuous lines represent alcoholics. STN, Subthalamic nucleus; L, left; R, right; Sup, superior; Inf, inferior.
Tables
- Table 1.
Location of regions where BPND (D2/D3 receptor availability) was significantly decreased by MP in controls and in alcoholics (pFWE-corrected = 0.05, small volume correction)a
Region Cluster t x y z Controls L striatum 6620 9.1 −30 2 −6 R striatum −22 −2 −4 R medial prefrontal 316 5.4 12 56 −2 14 60 14 L orbitofrontal 831 4.6 −14 32 −18 0 46 −18 L temporal 323 4.3 −60 −40 6 R prefrontal 439 4.1 38 48 28 L orbitofrontal 110 3.8 −38 26 −10 Alcoholics R striatum 2814 7.4 10 6 −10 L striatum −16 6 10 R orbitofrontal 232 4.7 2 52 −22 R temporal 187 4.6 66 −50 −2 L orbitofrontal 154 3.3 −14 32 −22 ↵aMNI coordinates (x, right left; y, anterior posterior; z, superior inferior) along with volume of the cluster (in voxels) and the t values for the comparisons.
L, Left; R, right.
- Table 2.
Location of regions where metabolism was significantly increased or decreased by MP in control subjects (pFWE-corrected = 0.05, small volume correction)a
Region BA Cluster t x y z Increases Cerebellum 14905 13.1 2 −54 −40 −2 −46 −18 L post-thalamus 230 4.9 24 −30 6 L lateral OFC 11, 47 651 4.3 −36 48 −22 −52 18 −6 R hippocampal 36 160 4.2 30 −42 2 L temporal pole 21, 38 272 4.2 −46 0 −48 R lateral OFC 11 293 3.9 30 60 −18 Decreases R medial frontal 11 670 6.1 12 40 −10 L medial frontal 10, 11 3462 5.6 −42 48 22 −28 16 62 R occipital 19 3299 5.1 46 −80 −18 R occipital 19 1291 5.0 4 −80 −14 R putamen 190 4.8 38 0 14 L insula 533 4.6 −42 −28 12 L temporal/parietal 37, 39 3342 4.6 −50 −70 −10 L caudate 381 4.4 −12 8 12 R postcentral 40 107 3.9 44 −36 38 R superior frontal 8 102 3.7 28 18 56 R caudate 158 3.6 14 12 10 L medial OFC 11 128 3.4 −10 58 −8 ↵aMNI coordinates (x, right left; y, anterior posterior; z, superior inferior) along with volume of the cluster (in voxels) and the t values for the comparisons.
L, Left; R, right.
- Table 3.
Location of regions where metabolism was significantly increased or decreased by MP in alcoholics (pFWE-corrected = 0.05, small volume correction)a
Region BA Cluster t x y z Increases R cerebellum 15620 11.2 42 −56 −38 R occipital 17, 18 112 4.2 22 −104 −4 L occipital 17 260 4.1 −2 −104 2 L post-thalamus 125 3.9 −20 −32 14 Midbrain 175 3.4 10 −10 −6 −10 −14 −10 L occipital 19 108 3.3 −26 −68 −8 Decreases R caudate/putamen 17495 5.8 18 18 −2 L caudate/putamen −10 16 0 Paracentral/precuneus 5, 7 −2 −28 66 R occipital 19 1955 4.7 44 −80 8 L occipital 19 2749 4.7 −62 −58 −6 R medial frontal 10 176 4.4 26 48 −10 L temporal pole 20, 21 319 4.4 −44 −34 −32 L temporal pole 21 315 3.6 −56 0 −40 Precuneus 7 106 3.6 −8 −56 36 R medial temporal 21 285 3.4 58 −28 8 R precentral 4, 6 304 3.3 34 −16 52 R precentral 4, 6 138 3.3 48 −28 58 R precentral 4, 6 128 3.1 62 −22 38 ↵aMNI coordinates (x, right left; y, anterior posterior; z, superior inferior) along with volume of the cluster (in voxels) and the t values for the comparisons.
L, Left; R, right.
- Table 4.
Locations where the SPM voxelwise analysis showed significant correlations between MP-induced changes in BPND and MP-induced changes in relative metabolism in controls (pu < 0.001)a
Region BA x y z t Thalamus VL 24 −16 8 9.73 Pons 6 −34 −20 8.9 Subthalamic 6 −18 −6 8.26 Rectal gyrus 25 2 20 −14 8.4 Parahippocampal 28 −10 −4 −16 6.02 Rectal gyrus 25 2 10 −16 5.93 Amygdala 34 −12 −8 −40 6.26 Parahippocampal 28 −20 2 −30 5.57 Parahippocampal 36 −26 −2 −34 5.12 ACC 24 −8 26 14 5.72 ACC 24 6 4 26 5.14 ACC 24 0 32 16 4.88 ↵aCorresponding BA and MNI coordinates (x, right left; y, anterior posterior; z, superior inferior) and the t values of the correlations.
VL, Ventrolateral.
- Table 5.
Locations where the SPM voxelwise analysis showed significant correlations between MP-induced changes in BPND and MP-induced changes in relative metabolism in alcoholics (pu < 0.001)a
Region BA x y z t Parahippocampal 36 30 0 −32 13.91 Insula 48 −46 −6 4 11.58 Lingual 27 8 −36 −8 11.1 Pons −2 −32 −12 7.81 ACC 24 −2 34 10 10.93 Medial OFC 11 0 38 −2 8.53 Medial OFC 11 −2 30 −6 8.06 ACC 24 10 28 18 10.48 ACC 32 8 36 20 9.04 Cerebellum −14 −30 −24 10.28 Insula 48 −44 6 0 8.32 Insula 48 −36 −16 14 7.67 Lateral OFC 45 48 20 −20 7.59 Lateral OFC 45 48 24 10 7.55 Frontal 47 40 30 4 4.97 SMA 6 2 −2 48 7.49 SMA 6 10 0 54 4.77 Precuneus 7 2 −66 40 7.23 Cuneus 23 6 −68 26 5.47 DLPFC 9 6 52 38 6.59 Medial frontal 10 8 58 32 6.16 Middle frontal 46 26 54 32 5.35 Middle OFC 11 8 68 −14 6.59 Middle OFC 11 12 58 −6 6.34 Medial frontal 10 6 64 20 5.79 Fusiform 20 40 −28 −26 6.39 Cerebellum 30 −42 −30 5.93 ↵aCorresponding BA and MNI coordinates (x, right left; y, anterior posterior; z, superior inferior) and the t values of the correlations.
SMA, Supplementary motor area; DLPFC, dorsolateral prefrontal cortex.
- Table 6.
Locations where SPM voxelwise correlations between MP-induced changes in BPND and changes in regional metabolism were significantly greater for alcoholics than controlsa
x y z Controls (r) Alcoholic (r) F, p L ACC −2 34 10 0.68 0.96 13, p < 0.0001 R ACC 10 28 18 0.52 0.94 8, p < 0.001 R ACC 8 36 20 0.46 0.93 9, p < 0.0001 Inferior frontal BA 45 48 24 10 0.43 0.87 9, p < 0.0001 Inferior frontal BA 45 40 30 4 −0.07 0.75 12, p < 0.0001 SMA BA 6 10 0 54 0.31 0.76 8, p < 0.002 Superior medial Frontal 6 52 38 0.07 0.81 11, p < 0.0001 8 58 32 −0.06 0.85 13, p < 0.0001 Middle OFC 8 68 −14 0.64 0.92 7, p < 0.004 Fusiform 40 −28 −26 0.41 0.87 9, p < 0.0001 Lingual 8 −36 −8 0.43 0.93 10, p < 0.0001 Parahippocampal 30 0 −32 0.01 0.95 10, p < 0.0001 Precuneus 2 −66 40 −0.02 0.79 8, p < 0.002 ↵aMNI coordinates (x, right left; y, anterior posterior; z, superior inferior), the correlation values (r) for the controls and the alcoholics, and the F values for the comparisons of the correlations and their significance level (p). None of the correlations in controls was greater than in alcoholics.
L, Left; R, right; SMA, supplementary motor area.
