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Control of dopamine communication by opioids: glutamate enters the discussion

Neuropsychopharmacology volume 48, pages 1833–1834 (2023)Cite this article

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Opioid use disorder (OUD) has become an increasingly widespread public health concern within the United States, affecting nearly 2.7 million individuals over the age of 12 [1]. This, coupled with a rise in opioid-related overdose deaths, has reinvigorated efforts to understand the intricacies of opioid interaction with the brain’s reward circuitry. While heroin, morphine, and related opioids have long been known to act through mu opioid receptors (MORs) to mediate the rewarding effects of these drugs, defining the cellular substrates at which MORs influence reward-seeking behavior remains an ongoing process.

In this issue, McGovern et al. investigate the roles that MORs located on ventral tegmental area (VTA) glutamate neurons play in opioid reward, and how they might mediate behavioral effects of the opioid oxycodone in male and female mice [2]. A decades old classic model of opioid function in the VTA and other brain areas (e.g., the hippocampus) suggests that principal output neurons like VTA dopamine (DA) neurons, or pyramidal neurons in the hippocampus, are excited through the process of ‘disinhibition’, whereby the activation of MORs by opioids inhibits GABA release onto the principal neurons [3]. This model of opioid action in VTA has since been incorporated into models seeking to define how opioids can produce DA-mediated drug reward.

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References

  1. Substance Abuse and Mental Health Services Administration. Key substance use and mental health indicators in the United States: Results from the 2020 National Survey on Drug Use and Health (HHS Publication No. PEP21-07-01-003, NSDUH Series H-56). Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. Rockville, MD. 2021.

  2. McGovern DJ, Polter AM, Prevost ED, Ly A, McNulty CJ, Rubinstein B, et al. Ventral tegmental area glutamate neurons establish a mu-opioid receptor gated circuit to mesolimbic dopamine neurons and regulate opioid-seeking behavior. Neuropsychopharmacology. 2023. https://doi.org/10.1038/s41386-023-01637-w.

  3. Johnson SW, North RA. Opioids excite dopamine neurons by hyperpolarization of local interneurons. J Neurosci. 1992;12:483–8.

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Funding

CRL and AFH are supported by the Intramural Research Program of NIH, NIDA.

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Authors and Affiliations

  1. U.S. Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse Intramural Research Program, Computational and Systems Neuroscience Branch, Electrophysiology Research Section, Baltimore, MD, 21224, USA

    Carl R. Lupica & Alexander F. Hoffman

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  1. Carl R. Lupica
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  2. Alexander F. Hoffman
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AFH wrote the initial draft. CRL reviewed, edited, and prepared the final submission. Both authors reviewed, edited, and approved the final version.

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Correspondence to Alexander F. Hoffman.

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Lupica, C.R., Hoffman, A.F. Control of dopamine communication by opioids: glutamate enters the discussion. Neuropsychopharmacol. 48, 1833–1834 (2023). https://doi.org/10.1038/s41386-023-01683-4

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