Neurochemistry of drug action

Abstract

Proton magnetic resonance spectroscopy ( 1 H MRS) is a non-invasive 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 (PET), single photon emission computed tomography (SPECT), and functional magnetic resonance imaging (fMRI). Drug abuse studies employing 1 H MRS have identified a number biochemical changes in the brain. The most consistent alterations across drug class were reductions in Nacetylaspartate and elevations in myo-inositol, while 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 impact 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.

Chronic and acute alcohol administration induced neurochemical changes in the brain: comparison of distinct zebrafish populations

“…GABA has been implicated in alcohol induced functional changes in the brain both in rodents (Feller et al, 1988) and in humans (Maccioni & Colombo, 2009). Reduced aspartate levels have been associated with the chronic use of alcohol in humans (Licata & Renshaw, 2010). Glycine receptors, which are ligand-gated chloride channels, are the primary targets of alcohol (Vengeliene et al, 2008).…”

Recovering from cocaine: Insights from clinical and preclinical investigations

“…This technique uses the properties of magnetic resonance to probe the neurochemical composition of the tissue being examined and is routinely used in academic hospitals to investigate tissue composition. While its reliability initially was limited to markers of neural health, inflammation and energy metabolism, such as creatine, myo-inositol, and N-acetylaspartate, it is now possible to isolate levels of glutamate and GABA (Licata and Renshaw, 2010) and can be applied to non-human primates as well as rodent models of addiction. Although it has not been a primary area of focus in this commentary, both glutamate and GABA are very important components to the maintenance of cocaine taking and are disrupted during abstinence.…”

The Directive 2010/63/EU on animal experimentation may skew the conclusions of pharmacological and behavioural studies

“…For the analysis of brain metabolites, compared to creatine-based ratio measurements, we favoured the use of a quantitative approach31 as the former may be sensitive to between group differences in creatine. The latter have been observed in studies entailing the administration of psychoactive compounds28.…”

“…MRS constitutes a powerful, non-invasive tool for monitoring neurobiological adjustments at both clinical and preclinical levels2728. We therefore performed a quantitative 1 H MRS examination in adult mice in hippocampus and prefrontal cortex, as these areas exhibit an elevated expression of CB1 receptors29 and are involved in individual responses to the administration and consumption of cannabinoids30.…”