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Abstract

Introduction Animal studies show that chronic cocaine use leads to decreased glutamate levels in the nucleus accumbens (NAcc), whereas drug‐seeking reinstatement is accompanied by enhanced glutamatergic transmission 1. However, little is known about such neurometabolic alterations in humans. We thus aim to investigate changes of the glutamate homeostasis in the NAcc of cocaine dependent individuals by means of a novel proton magnetic resonance spectroscopy (1H‐MRS) protocol that we have recently developed. Methods In 16 cocaine dependent individuals (CD) and 22 healthy controls (HC), non‐water suppressed PRESS localization 1H‐MRS preceded by a metabolite‐cycling pulse combined with inner‐volume saturation was performed on a 3T Philips Achieva System. MRS spectra were obtained from a voxel of 9.4x18.8x8.4mm, covering the anatomical dimensions of the left NAcc. For absolute quantification of the metabolites, a method based on the principle of reciprocity has been applied. Results An average signal‐to‐noise ratio of 16.97 and a mean line width of 6.93Hz (in single spectra) indicate good spectral quality. Metabolite concentrations of interest were quantified reliably using LCModel4 with Cramér‐Rao lower bounds<10. Moreover, glutamate concentrations in CDs (M=0.011, SD=0.001) were significantly reduced compared to HCs (M=0.013, SD=0.002), t(34)=3.81, p=.001, d=1.20. Discussion Despite the small voxel size, this novel 1H‐MRS protocol achieves high data quality and, thus, finally allows a reliable detection of glutamate in the human NAcc. For the first time this reveals that, in accordance with animal models, glutamatergic alterations occur in cocaine dependent humans and might play a decisive role in the development and maintenance of cocaine dependence.