ArticleBiological psychiatry2011
Impaired emotional-like behavior and serotonergic function during protracted abstinence from chronic morphine.
Article in Biological psychiatry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 151 citations in OpenAlex.
- Longitudinal changes of dopamine transporters in heroin users during abstinence.Psychopharmacology · 2015Trial
- Effects of oxycodone on tonic levels and phasic release of serotonin in the rat nucleus accumbens core.Bioelectrochemistry (Amsterdam, Netherlands) · 2026Article
- Spontaneous oxycodone withdrawal alters behavior and oligodendrocyte-related gene expression in mice.Pharmacology, biochemistry, and behavior · 2026Article
- The effects of low-dose ketamine and (2R,6R)-Hydroxynorketamine on affective behaviors associated with protracted oxycodone withdrawal.Psychopharmacology · 2026Article
- A widespread internal brain state for fentanyl withdrawal.bioRxiv : the preprint server for biology · 2026Article
- Negative affective states are not detected in rats following an intravenous self-administration regimen leading to incubation of oxycodone craving.bioRxiv : the preprint server for biology · 2026Article
- ECM remodeling in the mPFC exacerbates cocaine-induced hyperactivity and impairs threat vigilance.Translational psychiatry · 2026Article
- Propranolol Administration During Morphine Addiction Attenuates Reinstatement of Drug-Aversive Memories Caused by Exposure to Stressful Stimuli.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Disrupted circadian rhythms and opioid-mediated adverse effects: Bidirectional relationship and putative mechanisms.Journal of neuroendocrinology · 2025Review
- Prefrontal cortex excitatory neurons show distinct response to heroin-associated cue and social stimulus after prolonged heroin abstinence in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Disrupted maternal behavior in morphine-dependent pregnant rats and anhedonia in their offspring.Neuropharmacology · 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
- Incubation of social deficit during morphine abstinence in male mice using a novel unbiased and automatized method.Frontiers in behavioral neuroscience · 2025Article
- Disrupted Maternal Behavior in Morphine-Dependent Pregnant Rats and Anhedonia in their Offspring.bioRxiv : the preprint server for biology · 2024Article
- 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
- Model of negative affect induced by withdrawal from acute and chronic morphine administration in male mice.Scientific reports · 2024Article
- Role of α1-GABAJournal of psychopharmacology (Oxford, England) · 2024Article
- Cold nociception as a measure of hyperalgesia during spontaneous heroin withdrawal in mice.Pharmacology, biochemistry, and behavior · 2024Article
- Targeting mitochondrial dynamics of morphine-responsive dopaminergic neurons ameliorates opiate withdrawal.The Journal of clinical investigation · 2024Article
29 more citing papers are in PubMed but not listed here.
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7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundOpiate abuse is a chronic relapsing disorder, and maintaining prolonged abstinence remains a major challenge. Protracted abstinence is characterized by lowered mood, and clinical studies show elevated comorbidity between addiction and depressive disorders. At present, their relationship remains unclear and has been little studied in animal models. Here we investigated emotional alterations during protracted abstinence, in mice with a history of chronic morphine exposure.
methodsC57BL6J mice were exposed to a chronic intermittent escalating morphine regimen (20-100 mg/kg). Physical dependence (naloxone-precipitated withdrawal), despair-related behaviors (tail suspension test), and social behaviors were examined after 1 or 4 weeks of abstinence. Stress hormones and forebrain bioamine levels were analyzed at the end of morphine regimen and after 4 weeks of abstinence. Finally, we examined the effects of chronic fluoxetine during abstinence on morphine-induced behavioral deficits.
resultsAcute naloxone-induced withdrawal was clearly measurable after 1 week, and became undetectable after 4 weeks. In contrast, social and despair-related behaviors were unchanged after 1 week, but low sociability and despair-like behavior became significant after 4 weeks. Chronic morphine regimen increased both corticosterone levels and forebrain serotonin turnover, but only serotonergic activity in the dorsal raphe remained impaired after 4 weeks. Remarkably, chronic fluoxetine prevented depressive-like behavioral deficits in 4-week abstinent mice.
conclusionsDuring protracted abstinence, the immediate consequences of morphine exposure attenuate, whereas fluoxetine-sensitive emotional alterations strengthen with time. Our study establishes a direct link between morphine abstinence and depressive-like symptoms and strongly suggests that serotonin dysfunction represents a main mechanism contributing to mood disorders in opiate abstinence.
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