ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Cocaine dysregulates opioid gating of GABA neurotransmission in the ventral pallidum.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 52 citations in OpenAlex.
- Topiramate for cocaine dependence during methadone maintenance treatment: a randomized controlled trial.Drug and alcohol dependence · 2014Trial
- The neuroimmune-glutamate hypothesis of addiction.Neuroscience and biobehavioral reviews · 2026Review
- The influence of morphine treatment on the opioid propeptide gene expression in the forebrain of two inbred mouse strains with different sensitivity to opioids.Pharmacological reports : PR · 2025Article
- A review of the effects of different types of social behaviors on the recruitment of neuropeptides and neurotransmitters in the nucleus accumbens.Frontiers in neuroendocrinology · 2025Review
- Treadmill exercise training inhibits morphine CPP by reversing morphine effects on GABA neurotransmission in D2-MSNs of the accumbens-pallidal pathway in male mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Impaired striatal glutamate/GABA regulation in violent offenders with antisocial personality disorder and psychopathy.Molecular psychiatry · 2024Article
- Ventral pallidum GABA and glutamate neurons drive approach and avoidance through distinct modulation of VTA cell types.Nature communications · 2024Article
- Ventral pallidum GABA and glutamate neurons drive approach and avoidance through distinct modulation of VTA cell types.bioRxiv : the preprint server for biology · 2023Article
- Differential Modulation of GABAergic and Glutamatergic Neurons in the Ventral Pallidum by GABA and Neuropeptides.eNeuro · 2023Article
- Shared Mechanisms of GABAergic and Opioidergic Transmission Regulate Corticolimbic Reward Systems and Cognitive Aspects of Motivational Behaviors.Brain sciences · 2023Review
- Article
- Ventral pallidal regulation of motivated behaviors and reinforcement.Frontiers in neural circuits · 2023Review
- Dopamine D2 receptors bidirectionally regulate striatal enkephalin expression: Implications for cocaine reward.Cell reports · 2022Article
- Cocaine induces input and cell-type-specific synaptic plasticity in ventral pallidum-projecting nucleus accumbens medium spiny neurons.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- The role of enkephalinergic systems in substance use disorders.Frontiers in systems neuroscience · 2022Review
- Opioid Receptor-Mediated Regulation of Neurotransmission in the Brain.Frontiers in molecular neuroscience · 2022Review
- Article
- The Role of Mesostriatal Dopamine System and Corticostriatal Glutamatergic Transmission in Chronic Pain.Brain sciences · 2021Review
- Ventral pallidum DRD3 potentiates a pallido-habenular circuit driving accumbal dopamine release and cocaine seeking.Neuron · 2021Article
- Astrocytes in Addictive Disorders.Advances in neurobiology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The ventral pallidum (VP) is a target of dense nucleus accumbens projections. Many of these projections coexpress GABA and the neuropeptide enkephalin, a δ and μ opioid receptor (MOR) ligand. Of these two, the MOR in the VP is known to be involved in reward-related behaviors, such as hedonic responses to palatable food, alcohol intake, and reinstatement of cocaine seeking. Stimulating MORs in the VP decreases extracellular GABA, indicating that the effects of MORs in the VP on cocaine seeking are via modulating GABA neurotransmission. Here, we use whole-cell patch-clamp on a rat model of withdrawal from cocaine self-administration to test the hypothesis that MORs presynaptically regulate GABA transmission in the VP and that cocaine withdrawal changes the interaction between MORs and GABA. We found that in cocaine-extinguished rats pharmacological activation of MORs no longer presynaptically inhibited GABA release, whereas blocking the MORs disinhibited GABA release. Moreover, MOR-dependent long-term depression of GABA neurotransmission in the VP was lost in cocaine-extinguished rats. Last, GABA neurotransmission was found to be tonically suppressed in cocaine-extinguished rats. These substantial synaptic changes indicated that cocaine was increasing tone on MOR receptors. Accordingly, increasing endogenous tone by blocking the enzymatic degradation of enkephalin inhibited GABA neurotransmission in yoked saline rats but not in cocaine-extinguished rats. In conclusion, our results indicate that following withdrawal from cocaine self-administration enkephalin levels in the VP are elevated and the opioid modulation of GABA neurotransmission is impaired. This may contribute to the difficulties withdrawn addicts experience when trying to resist relapse.
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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.