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 dependencerelated 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.

Impaired learning from punishment of errors in smokers: Differences in dorsolateral prefrontal cortex and sensorimotor cortex blood-oxygen-level dependent responses

“…Merged data of cocaine dependent individuals and controls showed an effect of punishment magnitude in the sensorimotor cortex, with less activity for small losses, compared with medium and large losses. Controls alone exhibited the least activity for medium losses, implying that the low response to small losses was driven by cocaine dependent individuals (Rose et al, 2017). While these results initially imply a more appropriate comparative response to low punishments in cocaine dependent individuals, they may reflect overall lower punishment sensitivity.…”

dACC response to presentation of negative feedback predicts stimulant dependence diagnosis and stimulant use severity

“…Importantly, the present results demonstrated that SDIs' attenuated d/pgACC response following negative feedback occurred only when variance associated with prior behavior (and thus behavioral expectancies) was fully controlled. This effect is subtle, but may provide clarification to a nascent, and currently inconsistent, literature ( Parvaz et al, 2015 ; Patel et al, 2013 ; Rose et al, 2017 ). By controlling for expectancy effects, the task affords a pure measure of sensitivity to the mere presentation of negative feedback.…”

“… Patel et al (2013) failed to find cocaine-related dACC reductions during either phase of a MID task. Similarly, Rose et al (2017) failed to find any differences in dACC in cocaine users compared to controls, but did report reduced reward outcome-related responses in the right habenula in cocaine users. In contrast, a third study reported that cocaine-dependent individuals showed electrophysiological evidence of reduced sensitivity to unexpected, but not expected, error feedback on a gambling-type task ( Parvaz et al, 2015 ).…”

Cocaine addicted rats show reduced neural activity as revealed by manganese-enhanced MRI

“…This is in line with human data reporting brain hypo-functionality in cocaine addicts 4 , 5 , 20 , 21 , 30 , 68 , 69 . Cerebral hypoactivity has also been suggested as a biomarker of cocaine addiction as it is associated with reduced ability to experience reward 6 , 7 and control impulses 9 , 10 . It may also predict relapse risk 11 – 13 .…”

“…Specifically, a hypoactive brain state in addicted patients compared to healthy control has been demonstrated by functional neuroimaging studies 4 , 5 . In fact, brain hypoactivity is a suggested biomarker of cocaine addiction as it is associated with reduced ability to experience reward 6 , 7 and reduced ability to control impulses 8 – 10 . Brain hypoactivity also predicts relapse in abstinent patients and is as such seen as a determinant of relapse risk 11 – 13 .…”