ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
α2δ-1 signaling in nucleus accumbens is necessary for cocaine-induced relapse.
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 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
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- Astrocytic G Protein-Coupled Receptors in Drug Addiction.Engineering (Beijing, China) · 2025Article
- Astrocyte-Neuron Interactions in Substance Use Disorders.Advances in neurobiology · 2024Review
- Evaluation ofACS chemical neuroscience · 2023Article
- Astrocyte regulation of synaptic signaling in psychiatric disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Review
- α2δ-1 protein drives opioid-induced conditioned reward and synaptic NMDA receptor hyperactivity in the nucleus accumbens.Journal of neurochemistry · 2023Article
- Astrocytes in cocaine addiction and beyond.Molecular psychiatry · 2022Review
- Circuit selectivity in drug versus natural reward seeking behaviors.Journal of neurochemistry · 2021Review
- Cocaine Triggers Astrocyte-Mediated Synaptogenesis.Biological psychiatry · 2021Article
- Quiet on the Set! Astroglia Star in Silent Synaptogenesis and Cocaine Memory Formation.Biological psychiatry · 2021Article
- Gabapentinoid Benefit and Risk Stratification: Mechanisms Over Myth.Pain and therapy · 2020Review
- Review
- The Projection From Ventral CA1, Not Prefrontal Cortex, to Nucleus Accumbens Core Mediates Recent Memory Retrieval of Cocaine-Conditioned Place Preference.Frontiers in behavioral neuroscience · 2020Article
- Dynamic CRMP2 Regulation of CaV2.2 in the Prefrontal Cortex Contributes to the Reinstatement of Cocaine Seeking.Molecular neurobiology · 2020Article
- Gabapentin regulates dopaminergic neuron firing and theta oscillation in the ventral tegmental area to reverse depression-like behavior in chronic neuropathic pain state.Journal of pain research · 2018Article
- The Winding Road to Relapse: Forging a New Understanding of Cue-Induced Reinstatement Models and Their Associated Neural Mechanisms.Frontiers in behavioral neuroscience · 2018Review
- Cocaine Use Reverses Striatal Plasticity Produced During Cocaine Seeking.Biological psychiatry · 2017Article
- Neonatal Masculinization Blocks Increased Excitatory Synaptic Input in Female Rat Nucleus Accumbens Core.Endocrinology · 2016Article
- Fluoxetine Treatment Rescues Energy Metabolism Pathway Alterations in a Posttraumatic Stress Disorder Mouse Model.Molecular neuropsychiatry · 2016Article
- Glutamatergic transmission in drug reward: implications for drug addiction.Frontiers in neuroscience · 2015Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
Abstract
Relapse to cocaine seeking is associated with potentiated excitatory synapses in nucleus accumbens. α2δ-1 is an auxiliary subunit of voltage-gated calcium channels that affects calcium-channel trafficking and kinetics, initiates extracellular signaling cascades, and promotes excitatory synaptogenesis. Previous data demonstrate that repeated exposure to alcohol, nicotine, methamphetamine, and morphine upregulates α2δ-1 in reward-related brain regions, but it was unclear whether this alteration generalized to cocaine. Here, we show that α2δ-1 protein was increased in nucleus accumbens after cocaine self-administration and extinction compared with saline controls. Furthermore, the endogenous ligand thrombospondin-1, responsible for the synaptogenic properties of the α2δ-1 receptor, was likewise elevated. Using whole-cell patch-clamp recordings of EPSCs in nucleus accumbens, we demonstrated that gabapentin, a specific α2δ-1 antagonist, preferentially reduced the amplitude and increased the paired-pulse ratio of EPSCs evoked by electrical stimulation in slices from cocaine-experienced rats compared with controls. In vivo, gabapentin microinjected in the nucleus accumbens core attenuated cocaine-primed but not cue-induced reinstatement. Importantly, gabapentin's effects on drug seeking were not due to a general depression of spontaneous or cocaine-induced locomotor activity. Moreover, gabapentin had no effect on reinstatement of sucrose seeking. These data indicate that α2δ-1 contributes specifically to cocaine-reinstated drug seeking, and identifies this protein as a target for the development of cocaine relapse medications. These results also inform ongoing discussion in the literature regarding efficacy of gabapentin as a candidate addiction therapy.
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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.