Concentration of MP in plasma
The plasma levels of MP did not differ between the two conditions of administration. These levels corresponded for the cocaine-cue and the neutral video conditions respectively to 3 ±1 and 4 ±3 ng/ml at 30 minutes; to 7 ±3 and 7 ±4 ng/ml at 60 minutes; to 7 ±2 and 8 ±3 ng/ml at 90 minutes; and to 5 ±2 and 6 ±2 ng/ml at 120 minutes after its administration. The correlation between plasma MP concentration and the cardiovascular, behavioral and DA measures were not significant.
Effects of MP on the cardiovascular measures when exposed to the cocaine-video versus the neutral video
The changes in cardiovascular measures (pre – post / pre × 100) differed significantly between conditions for heart rate (Repeated ANOVA F=6, df 2, 59, p < 0.006), systolic (F= 11.6, p < 0.0001) and diastolic pressure (F=6.5 p < 0.004) (). Post hoc t test revealed that when compared with the baseline condition MP increased the cardiovascular measures when it was given with the cocaine-cue video for heart rate (7 ±8% increases, p < 0.0008), systolic (7 ±6% increases, p < 0.0001) and diastolic pressure (6 ±7% increases, p < 0.002); whereas when MP was given with the neutral-cue video none of the cardiovascular effects were significant (). Comparison between both MP conditions showed that MP’s cardiovascular effects were significantly greater when MP was given with the cocaine-cue than with the neutral-cue video for systolic (p < 0.01) and diastolic blood pressure (p < 0.03) but this difference did not reach significance for heart rate (p < 0.11).
Figure 1 Cardiovascular measures for the placebo neutral-cue, the MP neutral-cue and the MP cocaine-cue conditions. Significant increases in heart rate and systolic blood pressure were observed only for the MP cocaine-cue condition. Values correspond to means (more ...)
Effects of MP on craving when exposed to the cocaine-video versus the neutral video
The repeated ANOVA for the MP cocaine-cue video condition (resulted in significant increases in craving (df 2, 38; F = 16.4, p < 0.0001) whereas MP when given with the neutral-cue video condition did not change craving (df 2, 38; F = 1.5, p < 0.24) (). Post-hoc t tests for the MP cocaine-cue video condition revealed that craving was significantly greater for the post-MP/post-video measure than for the pre-MP/pre-video (df 19, t= 4.3, p < 0.0005) and the post-MP/pre-video measures (df 19, t= 4.2, p < 0.0005). The craving scores for the pre-MP/pre-video or post-MP/pre-video measures did not differ between the conditions (neutral-cue or the cocaine-cue video) (), which indicates that oral MP by itself does not increase craving and that it’s the exposure to the video that accounts for the difference in craving.
Figure 2 Average values on the Cocaine Craving Scale for the 3 conditions, before administration of the drug or placebo (Pre-drug/Pre-video), 55 minutes after administration of the drug but prior to video (Post-drug/Pre-video) and at the end of the video (Post-drug/Post-video). (more ...)
Effects of MP on [11C]raclopride binding when given with the cocaine-cue and the neutral videos
There were no differences between left and right regions for K1 or Bmax’/Kd’ and thus we report the results for the average scores in the left and right striatal and cerebellar regions. The K1 measure did not differ between conditions for any of the brain regions (). This indicates that the delivery of the tracer was not affected by MP (cocaine-cue or neutral-cue video conditions).
Table 2 Measures of K1 and Bmax/Kd in cerebellum (CBL), caudate (CDT), putamen (PUT) and ventral striatum (VST) for the [11C]raclopride measures taken after placebo with the neutral video (PL-Neutral), after MP with the cocaine cue video (MP-Cue) and after MP (more ...)
The Bmax’/Kd’ measures, which reflect D2 receptors that are not occupied by endogenous DA, differed significantly across conditions in caudate (F 6.1, p < 0.006), putamen (F 4.5, p < 0.02) and ventral striatum (F 3.9, p < 0.05). Post hoc t tests revealed that Bmax’/Kd’ measures when compared with the placebo-neutral condition were significantly reduced by MP in caudate both following the cocaine-cue (t = 2.5, df 19, p < 0.02) and the neutral-cue videos (t = 3.1, p < 0.006); in putamen following the neutral-cue (t = 2.8, p < 0.01) and showed a trend after the cocaine-cue video (t = 2.0, p < 0.06); and in ventral striatum after the neutral video (t = 2.4, p < 0.05) but did not differ for the cocaine-cue video. Comparison of Bmax/Kd measures between the cocaine–cue and the neutral-cue video conditions were not significant.
The correlations between DA changes and changes in cocaine craving as assessed with the CCQ were not significant for any of the MP conditions.
The SPM comparisons with the placebo neutral-cue video condition showed significant decreases (p < 0.01) in raclopride’s specific binding in dorsal striatum by oral MP both when given concomitantly with the neutral-cue video and when given with the cocaine-cue video (). Also when MP was given with the neutral-cue video, but not with the cocaine-cue video, SPM revealed decreases in binding in the ventral striatum. Though the SPM comparison between both MP conditions did not reach significance at p <0.01 a lowering of significance to p < 0.05 revealed that MP-induced decreases in the ventral striatum were significantly greater when co-administered with the neutral-cue video than with the cocaine-cue video ().
Figure 3 SPM results for the areas where the distribution volume ratio (DVR) for [11C]raclopride was significantly decreased by methylphenidate both when given with the cocaine-cue video and when given with the neutral-cue video as compared to the placebo neutral-cue (more ...)
Figure 4 SPM results for the areas where the changes in the distribution volume ratio (DVR) differed when MP was given with the neutral-cue than with the cocaine-cue video. Changes were greater in ventral striatum when MP was given with the neutral than the cocaine-cue (more ...)