ArticleNature neuroscience2016
Shifted pallidal co-release of GABA and glutamate in habenula drives cocaine withdrawal and relapse.
Article in Nature neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 90 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
90 citing papers in PubMed, 183 citations in OpenAlex.
- Light Therapy Alleviates Addiction-Related Symptoms and Reshapes Habenula and Midbrain Pathways.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Trial
- Beyond the role in motor function, entopeduncular nucleus, a critical neural hub in psychiatric disorders and sleep regulation.Annals of medicine · 2026Review
- Spatiotemporal remodeling in habenula marks the onset of depression-related phenotypes.Nature neuroscience · 2026Article
- Increased encoding of aversive stimuli by lateral habenula neurons during ΔNature communications · 2026Article
- A dual-pathway dysregulation in prefrontal-habenular circuits mediates stress susceptibility.Nature communications · 2026Article
- Brain-wide spatiotemporal mapping of glutamate/GABA dual-transmitter neurons during postnatal development in mice.Cell & bioscience · 2026Article
- Opioid withdrawal engages a habenular subpopulation responsive to aversive states.bioRxiv : the preprint server for biology · 2026Article
- Negative correlation between habenular volume and duration of gambling disorder: Modulation by symptom severity and personality traits.Journal of behavioral addictions · 2026Article
- Circuit-specific remodeling of synaptic co-transmission in stress-responsive networks.Animal cells and systems · 2026Review
- GABA-glutamate corelease is a mechanism for state-dependent neurotransmission.bioRxiv : the preprint server for biology · 2025Article
- Birds may represent a useful animal model for studying human mental disorders.Acta neuropsychiatrica · 2025Review
- Thalamus enables active dendritic coupling of inputs arriving at different cortical layers.Nature communications · 2025Article
- Inhibition mediated by group III metabotropic glutamate receptors regulates habenula activity and defensive behaviors.Nature communications · 2025Article
- Article
- Transcriptional complexity in the insect central complex: single nuclei RNA-sequencing of adult brain neurons derived from type 2 neuroblasts.bioRxiv : the preprint server for biology · 2025Article
- Remission from addiction: erasing the wrong circuits or making new ones?Nature reviews. Neuroscience · 2025Review
- Article
- Widespread co-release of glutamate and GABA throughout the mouse brain.Communications biology · 2024Article
- Glutamatergic neurons in ventral pallidum modulate heroin addiction via epithalamic innervation in rats.Acta pharmacologica Sinica · 2024Article
- Whole-brain connections of glutamatergic neurons in the mouse lateral habenula in both sexes.Biology of sex differences · 2024Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cocaine withdrawal produces aversive states and vulnerability to relapse, hallmarks of addiction. The lateral habenula (LHb) encodes negative stimuli and contributes to aversive withdrawal symptoms. However, it remains unclear which inputs to LHb promote this and what the consequences are for relapse susceptibility. We report, using rabies-based retrolabeling and optogenetic mapping, that the entopeduncular nucleus (EPN, the mouse equivalent of the globus pallidus interna) projects to an LHb neuronal subset innervating aversion-encoding midbrain GABA neurons. EPN-to-LHb excitatory signaling is limited by GABAergic cotransmission. This inhibitory component decreases during cocaine withdrawal as a result of reduced presynaptic vesicular GABA transporter (VGAT). This shifts the EPN-to-LHb GABA/glutamate balance, disinhibiting EPN-driven LHb activity. Selective virally mediated VGAT overexpression at EPN-to-LHb terminals during withdrawal normalizes GABAergic neurotransmission. This intervention rescues cocaine-evoked aversive states and prevents stress-induced reinstatement, used to model relapse. This identifies diminished inhibitory transmission at EPN-to-LHb GABA/glutamate synapses as a mechanism contributing to the relapsing feature of addictive behavior.
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What OpenQuestion holds
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.