ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2014
Distinct mu, delta, and kappa opioid receptor mechanisms underlie low sociability and depressive-like behaviors during heroin abstinence.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 87 citations in OpenAlex.
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- Anxiety-like behavior during protracted morphine withdrawal is driven by gut microbial dysbiosis and attenuated with probiotic treatment.Gut microbes · 2025Article
- VTA µ-Opioidergic Neurons Facilitate Low Sociability in Protracted Opioid Abstinence.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Emerging medications and pharmacological treatment approaches for substance use disorders.Pharmacology, biochemistry, and behavior · 2025Review
- Incubation of social deficit during morphine abstinence in male mice using a novel unbiased and automatized method.Frontiers in behavioral neuroscience · 2025Article
- The Dynorphin/-Opioid Receptor System at the Interface of Hyperalgesia/Hyperkatifeia and Addiction.Current addiction reports · 2025Review
- Chronic Morphine Leaves a Durable Fingerprint on Whole-Brain Functional Connectivity.Biological psychiatry · 2024Article
- VTA μ-opioidergic neurons facilitate low sociability in protracted opioid withdrawal.bioRxiv : the preprint server for biology · 2024Article
- Neuroscience in addiction research.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Cold nociception as a measure of hyperalgesia during spontaneous heroin withdrawal in mice.Pharmacology, biochemistry, and behavior · 2024Article
- Solving the Global Opioid Crisis: Incorporating Genetic Addiction Risk Assessment with Personalized Dopaminergic Homeostatic Therapy and Awareness Integration Therapy.Journal of addiction psychiatry · 2024Article
- Opioidergic tuning of social attachment: reciprocal relationship between social deprivation and opioid abuse.Frontiers in neuroanatomy · 2024Review
- Mu Opioid Receptor-Positive Neurons in the Dorsal Raphe Nucleus Are Impaired by Morphine Abstinence.Biological psychiatry · 2023Article
- Mu Opioid Receptor-Expressing Neurons in the Dorsal Raphe Nucleus Are Involved in Reward Processing and Affective Behaviors.Biological psychiatry · 2023Article
- Nucleus accumbens D1/D2 circuits control opioid withdrawal symptoms in mice.The Journal of clinical investigation · 2023Article
- Inhibition of dorsal raphe GABAergic neurons blocks hyperalgesia during heroin withdrawal.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Addiction is a chronic disorder involving recurring intoxication, withdrawal, and craving episodes. Escaping this vicious cycle requires maintenance of abstinence for extended periods of time and is a true challenge for addicted individuals. The emergence of depressive symptoms, including social withdrawal, is considered a main cause for relapse, but underlying mechanisms are poorly understood. Here we establish a mouse model of protracted abstinence to heroin, a major abused opiate, where both emotional and working memory deficits unfold. We show that delta and kappa opioid receptor (DOR and KOR, respectively) knockout mice develop either stronger or reduced emotional disruption during heroin abstinence, establishing DOR and KOR activities as protective and vulnerability factors, respectively, that regulate the severity of abstinence. Further, we found that chronic treatment with the antidepressant drug fluoxetine prevents emergence of low sociability, with no impact on the working memory deficit, implicating serotonergic mechanisms predominantly in emotional aspects of abstinence symptoms. Finally, targeting the main serotonergic brain structure, we show that gene knockout of mu opioid receptors (MORs) in the dorsal raphe nucleus (DRN) before heroin exposure abolishes the development of social withdrawal. This is the first result demonstrating that intermittent chronic MOR activation at the level of DRN represents an essential mechanism contributing to low sociability during protracted heroin abstinence. Altogether, our findings reveal crucial and distinct roles for all three opioid receptors in the development of emotional alterations that follow a history of heroin exposure and open the way towards understanding opioid system-mediated serotonin homeostasis in heroin abuse.
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