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G protein-coupled receptor modulation of striatal dopamine transmission: Implications for psychoactive drug effects

Mydirah Littlepage-Saunders

Mydirah Littlepage-Saunders

Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA

Neuroscience Graduate Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA

Contribution: Conceptualization (equal), Writing - original draft (equal), Writing - review & editing (equal)

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Michael J. Hochstein

Michael J. Hochstein

Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA

Contribution: Writing - original draft (equal), Writing - review & editing (supporting)

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Doris S. Chang

Doris S. Chang

Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA

Contribution: Writing - original draft (supporting), Writing - review & editing (equal)

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Kari A. Johnson

Corresponding Author

Kari A. Johnson

Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA

Neuroscience Graduate Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA

Correspondence

Kari A. Johnson, Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Email: [email protected]

Contribution: Conceptualization (lead), Writing - original draft (equal), Writing - review & editing (equal)

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First published: 31 May 2023

Abstract

Dopamine transmission in the striatum is a critical mediator of the rewarding and reinforcing effects of commonly misused psychoactive drugs. G protein-coupled receptors (GPCRs) that bind a variety of neuromodulators including dopamine, endocannabinoids, acetylcholine and endogenous opioid peptides regulate dopamine release by acting on several components of dopaminergic circuitry. Striatal dopamine release can be driven by both somatic action potential firing and local mechanisms that depend on acetylcholine released from striatal cholinergic interneurons. GPCRs that primarily regulate somatic firing of dopamine neurons via direct effects or modulation of synaptic inputs are likely to affect distinct aspects of behaviour and psychoactive drug actions compared with those GPCRs that primarily regulate local acetylcholine-dependent dopamine release in striatal regions. This review will highlight mechanisms by which GPCRs modulate dopaminergic transmission and the relevance of these findings to psychoactive drug effects on physiology and behaviour.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflicts of interest. M.L-S. and K.A.J. are employees of the US government, and this work was prepared as part of their official duties. Title 17 U.S.C. §105 provides that ‘Copyright protection under this title is not available for any work of the United States Government.’ Title 17 U.S.C. §101 defined a US government work as a work prepared by a military service member or employees of the US government as part of that person's official duties. The views in this article are those of the authors and do not necessarily reflect the views, official policy or position of the Uniformed Services University of the Health Sciences, the Henry M. Jackson Foundation for the Advancement of Military Medicine, the Armed Forces Radiobiology Research Institute, Department of the Navy, Department of Defense or the US federal government.

DATA AVAILABILITY STATEMENT

Data sharing is not applicable to this article because no new data were created or analysed in this study.