Glutamate Concentration of Medial Prefrontal Cortex is Inversely Associated with Addictive Behaviors: a Translational Study

Overview

Journal Transl Psychiatry

Specialties Psychiatry
Public Health

Date 2024 Oct 12

PMID 39396023

Authors

Hui Zhou

Tiantian Hong

Xi Chen

Conghui Su

Binyu Teng

Wan Xi

Jean Lud Cadet

Yihong Yang

Fengji Geng

Yuzheng Hu

Affiliations

Soon will be listed here.

Abstract

In both preclinical and clinical settings, dysregulated frontostriatal circuits have been identified as the underlying neural substrates of compulsive seeking/taking behaviors manifested in substance use disorders and behavioral addictions including internet gaming disorder (IGD). However, the neurochemical substrates for these disorders remain elusive. The lack of comprehensive cognitive assessments in animal models has hampered our understanding of neural plasticity in addiction from these models. In this study, combining data from a rat model of compulsive taking/seeking and human participants with various levels of IGD severity, we investigated the relationship between regional glutamate (Glu) concentration and addictive behaviors. We found that Glu levels were significantly lower in the prelimbic cortex (PrL) of rats after 20-days of methamphetamine self-administration (SA), compared to controls. Glu concentration after a punishment phase negatively correlated with acute drug-seeking behavior. In addition, changes in Glu levels from a drug naïve state to compulsive drug taking patterns negatively correlated with drug-seeking during both acute and prolonged abstinence. The human data revealed a significant negative correlation between Glu concentration in the dorsal anterior cingulate cortex (dACC), the human PrL counterpart, and symptoms of IGD. Interestingly, there was a positive correlation between Glu levels in the dACC and self-control, as well as mindful awareness. Further analysis revealed that the dACC Glu concentration mediated the relationship between self-control/mindful awareness and IGD symptoms. These results provide convergent evidence for a protective role of dACC/PrL in addiction, suggesting interventions to enhance dACC glutamatergic functions as a potential strategy for addiction prevention and treatment.

References

Tang Y, Holzel B, Posner M . The neuroscience of mindfulness meditation. Nat Rev Neurosci. 2015; 16(4):213-25. DOI: 10.1038/nrn3916. View

Luo X, Zhang S, Hu S, Bednarski S, Erdman E, Farr O . Error processing and gender-shared and -specific neural predictors of relapse in cocaine dependence. Brain. 2013; 136(Pt 4):1231-44. PMC: 3613717. DOI: 10.1093/brain/awt040. View

Provencher S . Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med. 1993; 30(6):672-9. DOI: 10.1002/mrm.1910300604. View

Ip I, Berrington A, Hess A, Parker A, Emir U, Bridge H . Combined fMRI-MRS acquires simultaneous glutamate and BOLD-fMRI signals in the human brain. Neuroimage. 2017; 155:113-119. PMC: 5519502. DOI: 10.1016/j.neuroimage.2017.04.030. View

Horder J, Petrinovic M, Mendez M, Bruns A, Takumi T, Spooren W . Glutamate and GABA in autism spectrum disorder-a translational magnetic resonance spectroscopy study in man and rodent models. Transl Psychiatry. 2018; 8(1):106. PMC: 5970172. DOI: 10.1038/s41398-018-0155-1. View

Duncan N, Enzi B, Wiebking C, Northoff G . Involvement of glutamate in rest-stimulus interaction between perigenual and supragenual anterior cingulate cortex: a combined fMRI-MRS study. Hum Brain Mapp. 2011; 32(12):2172-82. PMC: 6870441. DOI: 10.1002/hbm.21179. View

Mashhoon Y, Janes A, Jensen J, Prescot A, Pachas G, Renshaw P . Anterior cingulate proton spectroscopy glutamate levels differ as a function of smoking cessation outcome. Prog Neuropsychopharmacol Biol Psychiatry. 2011; 35(7):1709-13. PMC: 3303218. DOI: 10.1016/j.pnpbp.2011.05.006. View

Garland E, Howard M . Mindfulness-based treatment of addiction: current state of the field and envisioning the next wave of research. Addict Sci Clin Pract. 2018; 13(1):14. PMC: 5907295. DOI: 10.1186/s13722-018-0115-3. View

Hofmann W, Schmeichel B, Baddeley A . Executive functions and self-regulation. Trends Cogn Sci. 2012; 16(3):174-80. DOI: 10.1016/j.tics.2012.01.006. View

10.

Connolly C, Foxe J, Nierenberg J, Shpaner M, Garavan H . The neurobiology of cognitive control in successful cocaine abstinence. Drug Alcohol Depend. 2011; 121(1-2):45-53. PMC: 3262906. DOI: 10.1016/j.drugalcdep.2011.08.007. View

11.

Dong G, Wang M, Wang Z, Zheng H, Du X, Potenza M . Addiction severity modulates the precuneus involvement in internet gaming disorder: Functionality, morphology and effective connectivity. Prog Neuropsychopharmacol Biol Psychiatry. 2019; 98:109829. DOI: 10.1016/j.pnpbp.2019.109829. View

12.

Stagg C, Bestmann S, Constantinescu A, Moreno L, Allman C, Mekle R . Relationship between physiological measures of excitability and levels of glutamate and GABA in the human motor cortex. J Physiol. 2011; 589(Pt 23):5845-55. PMC: 3249054. DOI: 10.1113/jphysiol.2011.216978. View

13.

Zuo C, Davis K, Lukas S . Lower dACC glutamate in cannabis users during early phase abstinence. Neuropsychopharmacology. 2022; 47(11):1969-1975. PMC: 9485248. DOI: 10.1038/s41386-022-01321-5. View

14.

Ganji S, Banerjee A, Patel A, Zhao Y, Dimitrov I, Browning J . T2 measurement of J-coupled metabolites in the human brain at 3T. NMR Biomed. 2011; 25(4):523-9. PMC: 3852663. DOI: 10.1002/nbm.1767. View

15.

Dong G, DeVito E, Du X, Cui Z . Impaired inhibitory control in 'internet addiction disorder': a functional magnetic resonance imaging study. Psychiatry Res. 2012; 203(2-3):153-8. PMC: 3650485. DOI: 10.1016/j.pscychresns.2012.02.001. View

16.

Choi C, Coupland N, Bhardwaj P, Kalra S, Casault C, Reid K . T2 measurement and quantification of glutamate in human brain in vivo. Magn Reson Med. 2006; 56(5):971-7. DOI: 10.1002/mrm.21055. View

17.

Geramita M, van der Veen J, Barnett A, Savostyanova A, Shen J, Weinberger D . Reproducibility of prefrontal γ-aminobutyric acid measurements with J-edited spectroscopy. NMR Biomed. 2011; 24(9):1089-98. DOI: 10.1002/nbm.1662. View

18.

Sancho M, de Gracia M, Rodriguez R, Mallorqui-Bague N, Sanchez-Gonzalez J, Trujols J . Mindfulness-Based Interventions for the Treatment of Substance and Behavioral Addictions: A Systematic Review. Front Psychiatry. 2018; 9:95. PMC: 5884944. DOI: 10.3389/fpsyt.2018.00095. View

19.

Yang S, Salmeron B, Ross T, Xi Z, Stein E, Yang Y . Lower glutamate levels in rostral anterior cingulate of chronic cocaine users - A (1)H-MRS study using TE-averaged PRESS at 3 T with an optimized quantification strategy. Psychiatry Res. 2009; 174(3):171-6. PMC: 2788034. DOI: 10.1016/j.pscychresns.2009.05.004. View

20.

Le T, Potvin S, Zhornitsky S, Li C . Distinct patterns of prefrontal cortical disengagement during inhibitory control in addiction: A meta-analysis based on population characteristics. Neurosci Biobehav Rev. 2021; 127:255-269. PMC: 8411123. DOI: 10.1016/j.neubiorev.2021.04.028. View