Abstract
Treatment with N-acetylcysteine (NAC) normalizes glutamate (Glu) homeostasis and prevents relapse in drug-dependent animals. However, the effect of NAC on brain Glu levels in substance-dependent humans has not yet been investigated. Proton magnetic resonance spectroscopy ((1)H MRS) was used to investigate Glu changes in the dorsal anterior cingulate cortex (dACC) after a single dose of NAC in cocaine-dependent patients and normal controls. In an open-label, randomized, crossover study, 8 cocaine-dependent patients and 14 healthy controls underwent two scan sessions: one group receiving no compound and the other following a single administration of 2400 mg NAC. The Barratt Impulsiveness Scale was administered to examine the relation between dACC Glu levels and impulsivity. In the medication-free condition, Glu levels in the dACC were significantly higher in cocaine-dependent patients compared with healthy controls. After administration of NAC, Glu levels were reduced in the cocaine-dependent group, whereas NAC had no effect in healthy controls. Higher baseline Glu levels were associated with higher impulsivity, and both were predictive of greater NAC-induced Glu reduction. The current findings indicate that NAC can normalize elevated Glu levels in cocaine-dependent patients. These findings may have important implications for treatment, because abnormal Glu levels are related to relapse, and treatment with NAC prevented relapse in animal studies. Furthermore, clinical studies have indicated beneficial effects of NAC in cocaine-dependent patients, and the current study suggests that these beneficial effects might in part be mediated by the ability of NAC to normalize glutamatergic abnormalities.
Highlights
Research into the neurobiological substrate of drug addiction has focused on mesolimbic dopamine reward circuitry
Using 1H MRS, the current study is the first to demonstrate a significant reduction in Glu/creatine plus phosphocreatine (Cr) in the left dorsal ACC (dACC) by a single dose of NAC (2400 mg) in cocaine-dependent patients, whereas NAC had no effect on Glu relative to creatine (Glu/Cr) in healthy controls
In the medication-free condition, significant higher Glu/Cr was found in cocaine-dependent subjects compared with healthy controls, which normalized after a single administration of NAC
Summary
Research into the neurobiological substrate of drug addiction has focused on mesolimbic dopamine reward circuitry. In the medication-free condition, Glu levels in the dACC were significantly higher in cocaine-dependent patients compared with healthy controls.
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