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N ‐acetylcysteine reduces cocaine‐seeking behavior and anterior cingulate glutamate/glutamine levels among cocaine‐dependent individuals
Author(s) -
Woodcock Eric A.,
Lundahl Leslie H.,
Khatib Dalal,
Stanley Jeffrey A.,
Greenwald Mark K.
Publication year - 2021
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12900
Subject(s) - placebo , glutamine , psychology , glutamate receptor , priming (agriculture) , anesthesia , cocaine dependence , self administration , crossover study , medicine , pharmacology , psychiatry , addiction , chemistry , biochemistry , botany , alternative medicine , receptor , germination , amino acid , pathology , biology
N ‐acetylcysteine (NAC) is a cystine prodrug shown to reduce cocaine‐ and cue‐primed reinstatement of cocaine‐seeking behavior in preclinical studies. In this inpatient study, the effects of NAC maintenance versus placebo on cocaine‐seeking behavior were examined during cocaine‐primed and unprimed self‐administration sessions among non‐treatment‐seeking, cocaine‐dependent individuals. Twelve participants completed this double‐blind, placebo‐controlled, within‐subject crossover study. Each participant was maintained for 1 week (Sat–Fri) on NAC (1200‐mg TID; 3600 mg/day total) and 1 week on placebo (0‐mg TID); medication order was randomized. A subset of participants underwent proton magnetic resonance spectroscopy scans ( n = 8) on the third day of medication (Mon) to assess neurochemistry in the rostral anterior cingulate (rACC; voxel = 4.5 cm 3 ). In four randomized sessions (Tue–Fri) each week, each participant could earn unit amounts of cocaine (10 mg, fixed) versus money ($0.50 vs. $1.50) on a choice, progressive ratio schedule after insufflating active versus placebo cocaine‐priming doses (110 mg vs. 4 mg). Relative to the placebo priming dose, the active cocaine priming dose (110 mg) increased cocaine‐seeking behavior ( p = .003). NAC reduced cocaine‐primed cocaine‐seeking behavior compared with placebo levels ( p = .044) but did not alter placebo‐primed cocaine‐seeking behavior. The larger money alternative ($1.50) suppressed cocaine‐seeking behavior relative to the smaller money alternative ($0.50; p = .011). Compared with placebo levels, NAC significantly decreased rACC glutamate + glutamine levels ( p = .035) and numerically decreased rACC glutamate levels ( p = .085). These preliminary findings indicate that NAC suppresses cocaine‐seeking behavior in some, but not all, experimental scenarios. Further, our findings suggest NAC may exert its therapeutic effects by modulating excitatory tone in the rACC.