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

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.

Additive, synergic and antagonistic interactions between maternal immune activation and peripubertal stress in cocaine addiction-like behaviour, morphofunctional brain parameters and striatal transcriptome

“…This assertion is based on the striatal alterations we observed (increased glutamate levels due to decreased inhibition of glutamate release paralleled with increased striatal volume) which would also be consistent with a recent report that suggests that glutamate dynamics in the left putamen of people with a diagnosis of cocaine use disorder are predictive of their reported habit-like behaviour (i.e. the automaticity dimension of the Creature of Habit Scale) (32).…”

Characterizing cerebral metabolite profiles in anorexia and bulimia nervosa and their associations with habitual behavior

“…Disrupted glutamatergic signaling has been associated with automaticity (27) and disinhibition ( 64) in patients with substance use and neurodegenerative disorders, respectively. Although we provide novel evidence, linking ilPFC glutamate concentrations to habitual biases in AN-BP, this finding was not corrected for multiple comparisons and thus should be interpreted cautiously.…”

“…Reduced glutamate turnover in the putamen has been linked to greater habitual tendencies in patients with cocaine use disorder (27); however, it remains unknown if such an association would generalize to other regions implicated in habitual control. For example, the inferior lateral prefrontal cortex (ilPFC) has been shown to track both model-free (i.e., habitual) and model-based (goal-directed) systems, thus determining the relative control of each system over behavior (28).…”

Neurochemical substrates linked to impulsive and compulsive phenotypes in addiction: A preclinical perspective

“…This report and others (Wang et al, 2010) highlight the important role of NMDAR subunit composition on glutamatergic signalling and reward seeking. In humans, perturbations in glutamate concentration are reported in the NAcb (Engeli et al, 2020) and caudate putamen (Ersche et al, 2020) of substance dependent individuals.…”