Prefrontal GABA and glutamate levels correlate with impulsivity and cognitive function of prescription opioid addicts: A ¹H‐magnetic resonance spectroscopy study

Abstract

Aim: Prescription opioids are psychoactive substances that can elicit many neuropsychological effects. There are no studies that directly demonstrate the effects of prescription opioid addiction (POA) on the human brain. This study aimed to quantify γ-aminobutyric acid (GABA) and glutamate (Glu) levels in the prefrontal cortex (PFC) of POA patients using proton magnetic resonance spectroscopy ( 1 H-MRS), and to explore their association with impulsive behavior and cognitive impairment.Methods: Thirty-five patients with a definitive clinical diagnosis of codeine-containing cough syrup dependence and 35 matched healthy controls underwent neuropsychological assessments, namely the Barratt Impulsiveness Scale (BIS-11) and the Montreal Cognitive Assessment Scale (MoCA). Point-resolved spectroscopy was performed to detect GABA and glutamate within the medial PFC, and the corresponding levels were estimated using jMRUI and corrected for fraction of cerebrospinal fluid in the 1 H-MRS voxel. The difference in metabolite levels between groups and the correlation between metabolite levels and psychometric scores in patients were analyzed statistically.Results: The peak level predominantly consisting of GABA with a relatively small influence of other chemicals (GABA+) was lower and that of glutamate was higher in the PFC of POA patients than in healthy controls. GABA+ levels correlated negatively with BIS-11 scores but correlated positively with MoCA scores. In contrast, glutamate levels showed a positive correlation with BIS-11 scores but no significant correlation with MoCA scores. Conclusion:The quantitative in vivo measurement of GABA and glutamate levels in the PFC by 1 H-MRS could be a reliable way to evaluate impulsivity and cognitive function of POA.

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].…”

Neurochemical substrates linked to impulsive and compulsive phenotypes in addiction: A preclinical perspective

“…In humans, glutamate levels in the ACC, assessed using magnetic resonance spectroscopy (MRS), correlated positively with impulsive symptoms in subjects with attention-deficit hyperactivity disorder (ADHD) (Bauer et al, 2018;Ende et al 2016). Similar findings were found in relation to SUD using the Barratt Impulsiveness Scale (Li et al, 2020), which collectively highlight an involvement of glutamate signalling in prefrontal cortical regions in impulsive behaviour.…”

“…In the lateral OFC, but not the medial OFC, lower gene expression of the ɑ1 GABA A receptor subunit correlated with impulsive action but not impulsive choice in rats (Ucha et al, 2019). In humans, reduced MRS-GABA levels in the PFC correlated with risky and impulsive decision making (Boy et al, 2011;Weidacker et al, 2020), with Barratt Impulsiveness Scale impulsivity scores correlating negatively with MRS GABA levels in the PFC and ACC (Ende et al 2016;Li et al, 2020). Finally, reductions in GABA levels in the inferior frontal gyrus were found to underlie SSRT impulsivity (Murley et al, 2020), suggesting that multiple subtypes of impulsivity implicate diminished GABA-ergic function in several cortico-striatal regions.…”

Network Pharmacology Dissection of Multi-scale Mechanisms of Action of Tu-Xian Mixture for the Treatment of Diabetic Cognitive Impairment

“…Brain excitement suppresses imbalance induced by γ-aminobutyric acid system dysfunction is an important mechanism for cognitive impairment [47,48]. The levels of γ-aminobutyric acid in the brain of patients with opioid addiction were significantly reduced, which was positively related to cognitive impairment [49]. Alpha-asarone, the major ingredient isolated from the Chinese medicinal herb Acorus tatarinowii Schott, can improve the cognitive function of AD rats by enhancing the γ-aminobutyric acid system, inhibiting the overexcitation of hippocampal neurons, and reducing the deposition of amyloid β-protein (Aβ) [50].…”