Dissociable Effects of Cocaine Dependence on Reward Processes: The Role of Acute Cocaine and Craving

Abstract

The relative impact of chronic vs acute cocaine on dependence-related variability in reward processing in cocaine-dependent individuals (CD) is not well understood, despite the relevance of such effects to long-term outcomes. To dissociate these effects, CD (N=15) and healthy controls (HC; N=15) underwent MRI two times while performing a monetary incentive delay task. Both scans were identical across subjects/groups, except that, in a single-blind, counterbalanced design, CD received intravenous cocaine (30 mg/70 kg) before one session (CD+cocaine) and saline in another (CD+saline). Imaging analyses focused on activity related to anticipatory valence (gain/loss), anticipatory magnitude (small/medium/large), and reinforcing outcomes (successful/unsuccessful). Drug condition (cocaine vs saline) and group (HC vs CD+cocaine or CD+saline) did not influence valence-related activity. However, compared with HC, magnitude-related activity for gains was reduced in CD in the left cingulate gyrus post-cocaine and in the left putamen in the abstinence/saline condition. In contrast, magnitude-dependent activity for losses increased in CD vs HC in the right inferior parietal lobe post-cocaine and in the left superior frontal gyrus post-saline. Across outcomes (ie, successful and unsuccessful) activity in the right habenula decreased in CD in the abstinence/saline condition vs acute cocaine and HC. Cocaine-dependent variability in outcome- and loss-magnitude activity correlated negatively with ratings of cocaine craving and positively with how high subjects felt during the scanning session. Collectively, these data suggest dissociable effects of acute cocaine on non-drug reward processes, with cocaine consumption partially ameliorating dependence-related insensitivity to reinforcing outcomes/'liking', but having no discernible effect on dependence-related alterations in incentive salience/'wanting'. The relationship of drug-related affective sequelae to non-drug reward processing suggests that CD experience a general alteration of reward function and may be motivated to continue using cocaine for reasons beyond desired drug-related effects. This may have implications for individual differences in treatment efficacy for approaches that rely on reinforcement strategies (eg, contingency management) and for the long-term success of treatment.

Figure 1

Experimental paradigm and timeline. (a) Revised monetary incentive delay (MID.R) paradigm. Note: x denotes a variable presentation time, where x₁ and x₂ sum to 4000 ms; x₄ is a wait period with duration equal to the difference between x₃ and 250 ms. (b) Timing of cocaine injection relative to MID.R performance. (c) Plasma levels of cocaine (ng/ml) during practice performance of the MID.R.

Figure 2

Group-dependent effects on magnitude-related activity. (a) Interaction between group (HC vs CD+cocaine) and gain magnitude (left cingulate gyrus/BA32; SVC analysis; cluster extent (K_E)=47). (b) Main effect of group (HC vs CD+saline) on gain magnitude-related activity (left putamen; SVC analysis; K_E=51). (c) Interaction between group (HC vs CD+cocaine) and loss magnitude (right inferior parietal lobe/BA40; WB analysis; K_E=238). (d) Main effect of group (HC vs CD+saline) on loss of magnitude-related activity (left superior frontal gyrus; WB analysis; K_E=283). Note: *p_CORRECTED<0.05. Error bars show ±1 SE; activation maps are rendered on the ICBM452 T1 template from AFNI; right=left; minimum corrected K_E=200 for WB and 47 for SVC analyses; see Supplementary Figures S4A and B for task-dependent activity distributions corresponding to these significant effects.

Figure 3

Group- and condition-dependent effects on outcome-related activity in the right habenula. (a) condition × outcome interaction (WB analysis; K_E=223); (b) condition × outcome interaction (SVC analysis; K_E=177); (c) Main effect of group (HC vs CD+saline; SVC analysis; K_E=51); (d) group (HC vs CD+saline) × outcome interaction (SVC analysis; K_E=67). Note: *=p_CORRECTED<0.05. Error bars show ±1 SE; activation maps are rendered on the ICBM452 T1 template from AFNI; right=left; minimum corrected K_E=200 for WB and 47 for SVC; see Supplementary Figure S4C for task-dependent activity distributions corresponding to these significant effects.

Figure 4

Correlations between group- and condition-dependent variability in brain function and affective ratings. Significant associations with activity are shown for: (a) group-dependent differences in magnitude-related activity in the left superior frontal gyrus/BA6 for CD+saline only and (i) craving and (ii) high (WB analysis); and (b) outcome-related differences in function in the right habenula for success-related activity in CD+cocaine and CD+saline and ratings of (i) high and (ii) craving (WB analysis) and across outcomes for CD+saline only and (iii) craving (SVC analysis). Note: All p<0.05; *p_CORRECTED<0.0125.