Neurochemistry of drug action: insights from proton magnetic resonance spectroscopic imaging and their relevance to addiction

Abstract

Proton magnetic resonance spectroscopy ((1)H MRS) is a noninvasive imaging technique that permits measurement of particular compounds or metabolites within the tissue of interest. In the brain, (1)H MRS provides a snapshot of the neurochemical environment within a defined volume of interest. A search of the literature demonstrates the widespread utility of this technique for characterizing tumors, tracking the progress of neurodegenerative disease, and for understanding the neurobiological basis of psychiatric disorders. As of relatively recently, (1)H MRS has found its way into substance abuse research, and it is beginning to become recognized as a valuable complement in the brain imaging toolbox that also contains positron emission tomography, single-photon-emission computed tomography, and functional magnetic resonance imaging. Drug abuse studies using (1)H MRS have identified several biochemical changes in the brain. The most consistent alterations across drug class were reductions in N-acetylaspartate and elevations in myo-inositol, whereas changes in choline, creatine, and amino acid transmitters also were abundant. Together, the studies discussed herein provide evidence that drugs of abuse may have a profound effect on neuronal health, energy metabolism and maintenance, inflammatory processes, cell membrane turnover, and neurotransmission, and these biochemical changes may underlie the neuropathology within brain tissue that subsequently gives rise to the cognitive and behavioral impairments associated with drug addiction.

Figure 1

Proton spectrum acquired at 4 tesla from a 16cc voxel within the parieto-occipital cortex of a 26-year old healthy male volunteer. Cho/PCho: choline/phosphocholine, Cr/PCr: creatine/phosphocreatine, GABA: γ-aminobutyric acid, Glx: glutamate/glutamine, GSH: glutathione, H2O: water, Lac: lactate, mI: myo-inositol, MM: macromolecules, NAA: N-acetylaspartate, NAAG: N-acetylaspartylglutamate, Scy: scyllo-inositol, Tau: taurine. [Courtesy of J. Eric Jensen, Ph.D., Brain Imaging Center, McLean Hospital/Harvard Medical School].