ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2022
Involvement of the ghrelin system in the maintenance and reinstatement of cocaine-motivated behaviors: a role of adrenergic action at peripheral β1 receptors.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Animal studies reveal that the ghrelin pathway regulates alcohol-mediated responses.Frontiers in psychiatry · 2023Pooled it
- Effects of Fentanyl-Adulterated Methamphetamine on Circulating Ghrelin in Rats.International journal of molecular sciences · 2025Article
- Beyond Hunger: The Structure, Signaling, and Systemic Roles of Ghrelin.International journal of molecular sciences · 2025Review
- Neuroendocrinology meets addiction: Emerging pharmacotherapies on the horizon.Journal of internal medicine · 2025Review
- Novel potential pharmacological approaches in treating eating disorders comorbid with substance use disorders.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Review
- Environmental enrichment attenuates reinstatement of heroin seeking and reverses heroin-induced upregulation of mesolimbic ghrelin receptors.Drug and alcohol dependence · 2025Article
- Effects of Fentanyl-Laced Cocaine on Circulating Ghrelin, Insulin, and Glucose Levels in Rats.International journal of molecular sciences · 2025Article
- GHSR blockade, but not reduction of peripherally circulating ghrelin via βMolecular psychiatry · 2025Article
- Divergent transcriptomic profiles in depressed individuals with hyper- and hypophagia implicating inflammatory status.Journal of psychiatric research · 2024Article
- Recent advances in drug discovery efforts targeting the sigma 1 receptor system: Implications for novel medications designed to reduce excessive drug and food seeking.Addiction neuroscience · 2023Article
- Paternal methamphetamine exposure induces higher sensitivity to methamphetamine in male offspring through driving ADRB1 on CaMKII-positive neurons in mPFC.Translational psychiatry · 2023Article
- Metabolic hormone action in the VTA: Reward-directed behavior and mechanistic insights.Physiology & behavior · 2023Review
- Initial Pharmacological Characterization of a Major Hydroxy Metabolite of PF-5190457: Inverse Agonist Activity of PF-6870961 at the Ghrelin Receptor.The Journal of pharmacology and experimental therapeutics · 2023Article
- From the stomach to locus coeruleus: new neural substrate for ghrelin's effects on ingestive, motivated and anxiety-like behaviors.Frontiers in pharmacology · 2023Article
- Ghrelin receptor antagonist JMV2959 blunts cocaine and oxycodone drug-seeking, but not self-administration, in male rats.Frontiers in pharmacology · 2023Article
- The Role of Ghrelin/GHS-R1A Signaling in Nonalcohol Drug Addictions.International journal of molecular sciences · 2022Review
- Ghrelin mediated regulation of neurosynaptic transmitters in depressive disorders.Current research in pharmacology and drug discovery · 2022Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Cocaine addiction is a significant medical and public concern. Despite decades of research effort, development of pharmacotherapy for cocaine use disorder remains largely unsuccessful. This may be partially due to insufficient understanding of the complex biological mechanisms involved in the pathophysiology of this disorder. In the present study, we show that: (1) elevation of ghrelin by cocaine plays a critical role in maintenance of cocaine self-administration and cocaine-seeking motivated by cocaine-conditioned stimuli; (2) acquisition of cocaine-taking behavior is associated with the acquisition of stimulatory effects of cocaine by cocaine-conditioned stimuli on ghrelin secretion, and with an upregulation of ghrelin receptor mRNA levels in the ventral tegmental area (VTA); (3) blockade of ghrelin signaling by pretreatment with JMV2959, a selective ghrelin receptor antagonist, dose-dependently inhibits reinstatement of cocaine-seeking triggered by either cocaine or yohimbine in behaviorally extinguished animals with a history of cocaine self-administration; (4) JMV2959 pretreatment also inhibits brain stimulation reward (BSR) and cocaine-potentiated BSR maintained by optogenetic stimulation of VTA dopamine neurons in DAT-Cre mice; (5) blockade of peripheral adrenergic β1 receptors by atenolol potently attenuates the elevation in circulating ghrelin induced by cocaine and inhibits cocaine self-administration and cocaine reinstatement triggered by cocaine. These findings demonstrate that the endogenous ghrelin system plays an important role in cocaine-related addictive behaviors and suggest that manipulating and targeting this system may be viable for mitigating cocaine use disorder.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.