Quantifying absolute glutamate concentrations in nucleus accumbens of prescription opioid addicts by using ¹H MRS

Abstract

Introduction The diagnosis of psychoactive substance use disorders has been based primarily on descriptive, symptomatic checklist criteria. In opioid addiction, there are no objective biological indicators specific enough to guide diagnosis, monitor disease status, and evaluate efficacy of therapeutic interventions. Proton magnetic resonance spectroscopy ( 1 H MRS) of the brain has potential to identify and quantify biomarkers for the diagnosis of opioid dependence. The purpose of this study was to detect the absolute glutamate concentration in the nucleus accumbens (NAc) of patients with prescription opioid dependence using 1 H MRS, and to analyze its clinical associations. Methods Twenty patients with clinically diagnosed definitive prescription opioid dependent (mean age = 26.5 ± 4.3 years) and 20 matched healthy controls (mean age = 26.1 ± 3.8 years) participated in this study. Patients were evaluated with the Barratt Impulsiveness Scale (BIS‐11), the Self‐Rating Anxiety Scale (SAS), and the opiate Addiction Severity Inventory (ASI). We used point‐resolved spectroscopy to quantify the absolute concentrations of metabolites (glutamate, choline, N ‐acetylaspartate, glutamine, creatine) within the NAc. The difference between metabolite levels of groups and Pearson's correlation between glutamate levels and psychometric scores in patients were analyzed statistically. Results Glutamate concentrations in the NAc were significantly higher in prescription opiate addicts than in controls ( t = 3.84, p = .001). None of the other metabolites differed significantly between the two groups (all p s > .05). The glutamate concentrations correlated positively with BIS‐11 scores in prescription opiate addicts ( r = .671, p = .001), but not with SAS score and ASI index. Conclusions Glutamate levels in the NAc measured quantitatively with in vivo 1 H MRS could be used as a biomarker to evaluate disease condition in opioid‐dependent patients.

No evidence of abnormal metabolic or inflammatory activity in the brains of patients with rheumatoid arthritis: results from a preliminary study using whole-brain magnetic resonance spectroscopic imaging (MRSI)

“…Benzodiazepines and non-benzodiazepine sedative-hypnotics can change body temperature in animal models [31,32] and brain glutamine synthesis [33], but effects on brain temperature, NAA, CHO, or MI have not been reported [34]. Opioids similarly have been shown to affect brain glutamate in reward system areas [35][36][37][38], but not NAA, CHO, or MI. Two human studies have found reduced NAA in frontal gray matter in opioid addicted individuals [39,40].…”

Reliability of Glutamate Quantification in Human Nucleus Accumbens Using Proton Magnetic Resonance Spectroscopy at a 70-cm Wide-Bore Clinical 3T MRI System

“…In sum, our study is the first which involved that high quality glutamate spectrum can reliability be obtained from a ~3.4 cm 3 nucleus accumbens voxel using a 70-cm wide-bore clinical 3T MRI system with the short-echo-time PRESS. Studies using 1 H-MRS have reported differences in glutamatergic neurotransmitter concentrations in nucleus accumbens between healthy and clinical populations such as alcohol-dependent or opioid-dependent (Bauer et al, 2013 ; Liu et al, 2017 ). Reliable quantification of glutamate using 1 H-MRS with a wide-bore clinical 3T MRI system would be beneficial for clinical studies relating to glutamate in the human nucleus accumbens.…”

The Opioid-Addicted Tetrapartite Synapse

“…Although dopamine strongly contributes to the reinforcing properties of all drugs of abuse including opioids [reviewed in (31)], a robust literature implicates dysregulated homeostasis at glutamatergic synapses in OUD-associated cognitive impairments and cue reactivity (i.e., craving) (32,33). For example, glutamate levels measured by magnetic resonance spectroscopy in reward-associated brain regions in opioid-dependent users correlate positively with measures of impulsivity (34), and opioid-conditioned cues evoke craving in parallel with functional magnetic resonance imaging measures of increased activity in corticostriatal and amygdalostriatal glutamatergic circuits (35). In this review, we explore the preclinical data that identify the cellular underpinnings of these OUD-induced glutamatergic adaptations found in human imaging studies.…”