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Abstract:
Introduction
Data from animal studies show that chronic administration of cocaine leads to decreased levels of glutamate (Glu) in the nucleus accumbens (NAcc); whereas drug-seeking reinstatement is associated with enhanced glutamatergic transmission. However, little is known about neurometabolic changes
in humans, mainly due to previous methodological restrictions. We thus aim to investigate the changes associated with chronic cocaine use on Glu homeostasis in NAcc of human subjects using a proton magnetic resonance spectroscopy (1H-MRS) protocol that we have recently developed. 1 H-MRS allows for the quantification of brain metabolites such as Glu even within small subcortical
volumes that have been difficult to assess in humans yet. The aim of this pilot study was to verify the intra-
individual consistency of metabolic concentrations in NAcc over time by sequential 1 H-MRS measurements.
Methods
To detect potential individual fluctuation, five non-water
suppressed PRESS localization combined with inner-volume saturation was performed in one healthy volunteer at five different time points. MRS spectra were obtained from the left NAcc as the region of interest (voxel size=9.4x18.8x8.4mm). Metabolite concentrations ratios to
creatine (Cr) based on fitting results (LCModel) with Cramer-Rao lower bounds lower than 20 were considered as reliable.
Results
Average spectra (n=5), LCModel fit, and the fit-residual of the five measurement time points indicate good spectral quality. The metabolic concentration ratios over all measurement points as shown in Cr, N-acetyl-aspartate (NAA), glutamate (Glu) and the combination of Glu and glutamine (Glx), and choline (Cho) could be quantified reliably and were stable over time.
Discussion
Despite small voxel size, the proposed method allows the detection of metabolite markers in NAcc with high data quality. Furthermore, intra-individual metabolic concentrations remain relatively constant and thus, providing a feasible measure for differences between healthy controls and cocaine users especially in regard to glutamatergic alterations observed in preclinical models.
