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other·preclinical research, biomedical research, neurology, psychiatry·PMC10545966

Ghrelin receptor antagonist JMV2959 blunts cocaine and oxycodone drug-seeking, but not self-administration, in male rats

Frontiers in Pharmacology · 7 authors, 2 centres

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TL;DR

This preclinical study tested whether blocking the ghrelin receptor alters cocaine and oxycodone intake and seeking in male rats. The blocker JMV2959 did not affect drug self-administration but significantly reduced cue-induced drug-seeking.

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This preclinical study investigated the effects of the ghrelin receptor (GHS1αR) antagonist JMV2959 on cocaine and oxycodone-related behaviors in male Sprague-Dawley rats. The study found that JMV2959 did not alter the self-administration of either drug. The authors note that the doses used may have been below the threshold to affect reinforcement and that other experimental variables could explain discrepancies with prior studies. The findings suggest the ghrelin-GHS1αR axis may regulate overlapping relapse-like mechanisms for both psychostimulants and opioids, warranting further investigation into its potential as a therapeutic target.

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other

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preclinical research

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ORIGINAL PAPER

PMC10545966

Ghrelin receptor antagonist JMV2959 blunts cocaine and oxycodone drug-seeking, but not self-administration, in male rats

Frontiers in Pharmacology

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ABSTRACT

The drug overdose crisis has spawned serious health consequences, including the increased incidence of substance use disorders (SUDs), conditions manifested by escalating medical and psychological impairments. While medication management is a key adjunct in SUD treatment, this crisis has crystallized the need to develop additional therapeutics to facilitate extended recovery from SUDs. The “hunger hormone” ghrelin acts by binding to the growth hormone secretagogue receptor 1α (GHS1αR) to control homeostatic and hedonic aspects of food intake and has been implicated in the mechanisms underlying SUDs. Preclinical studies indicate that GHS1αR antagonists and inverse agonists suppress reward-related signaling associated with cocaine and opioids. In the present study, we found that the GHS1αR antagonist JMV2959 was efficacious to suppress both cue-reinforced cocaine and oxycodone drug-seeking, but not cocaine or oxycodone self-administration in male Sprague-Dawley rats. These data suggest a role of the ghrelin-GHS1αR axis in mediating overlapping reward-related aspects of cocaine and oxycodone and premises the possibility that a GHS1αR antagonist may be a valuable therapeutic strategy for relapse vulnerability in SUDs.

CITATION EXPORT

Christina R. Merritt, Erik J. Garcia, Victoria D. Brehm et al.. Ghrelin receptor antagonist JMV2959 blunts cocaine and oxycodone drug-seeking, but not self-administration, in male rats. Frontiers in Pharmacology. (2023). https://doi.org/10.3389/fphar.2023.1268366

AUTHORS

7 · 2 CENTRES

Christina R. Merritt, Erik J. Garcia, Victoria D. Brehm, Robert G. Fox, F. Gerard Moeller, Noelle C. Anastasio, Kathryn A. Cunningham

1 Center for Addiction Sciences and Therapeutics and Department of Pharmacology and Toxicology, John Sealy School of Medicine, University of Texas Medical Branch, Galveston, TX, United States
2 C. Kenneth and Dianne Wright Center for Clinical and Translational Research, Departments of Psychiatry and Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, United States