Reduced Glutamate Turnover in the Putamen Is Linked With Automatic Habits in Human Cocaine Addiction

Ersche, K.D. and Lim, T.V. and Murley, A.G. and Rua, C. and Vaghi, Matilde M. and White, T.L. and Williams, G.B. and Robbins, T.W. (2021) Reduced Glutamate Turnover in the Putamen Is Linked With Automatic Habits in Human Cocaine Addiction. Biological Psychiatry 89 (10), pp. 970-979. ISSN 0006-3223.

Abstract

Background: The balance between goal-directed behavior and habits has been hypothesized to be biased toward the latter in individuals with cocaine use disorder (CUD), suggesting possible neurochemical changes in the putamen, which may contribute to their compulsive behavior. Methods: We assessed habitual behavior in 48 patients with CUD and 42 healthy control participants using a contingency degradation paradigm and the Creature of Habit Scale. In a subgroup of this sample (CUD: n = 21; control participants: n = 22), we also measured glutamate and glutamine concentrations in the left putamen using ultra-high-field (7T) magnetic resonance spectroscopy. We hypothesized that increased habitual tendencies in patients with CUD would be associated with abnormal glutamatergic metabolites in the putamen. Results: Compared with their non–drug-using peers, patients with CUD exhibited greater habitual tendencies during contingency degradation, which correlated with increased levels of self-reported daily habits. We further identified a significant reduction in glutamate concentration and glutamate turnover (glutamate-to-glutamine ratio) in the putamen in patients with CUD, which was significantly related to the level of self-reported daily habits. Conclusions: Patients with CUD exhibit enhanced habitual behavior, as assessed both by questionnaire and by a laboratory paradigm of contingency degradation. This automatic habitual tendency is related to a reduced glutamate turnover in the putamen, suggesting a dysregulation of habits caused by chronic cocaine use.

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