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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.
