ArticleFrontiers in molecular neuroscience2012
Calcium-permeable AMPA receptors in the VTA and nucleus accumbens after cocaine exposure: when, how, and why?
Article in Frontiers in molecular neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers.
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Who cites it
150 citing papers in PubMed, 203 citations in OpenAlex.
- The neuroimmune-glutamate hypothesis of addiction.Neuroscience and biobehavioral reviews · 2026Review
- Effects of withdrawal from intermittent vs. long access cocaine self-administration on nucleus accumbens calcium permeable AMPA receptor transmission and incubation of craving in female and male rats.Psychopharmacology · 2026Article
- Association between aperiodic activity and impulsivity in individuals with methamphetamine use disorder.Psychopharmacology · 2026Article
- Sleep regulates drug seeking and relapse - a perspective.Molecular psychiatry · 2026Review
- Heterosynaptic Interactions between the Dorsal and Ventral Hippocampus in Individual Medium Spiny Neurons of the Nucleus Accumbens Ventromedial Shell.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Selective impairment of long-term depression in accumbal D1-MSNs involves calcium-permeable AMPARs in Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Dissociating the incubation of appetitive and consummatory behavior in a model of oral cocaine self-administration.Pharmacology, biochemistry, and behavior · 2025Article
- Retinoic acid-mediated homeostatic plasticity drives cell type-specific CP-AMPAR accumulation in nucleus accumbens core and incubation of cocaine craving.Molecular psychiatry · 2025Article
- Changes in nucleus accumbens core translatome accompanying incubation of cocaine craving.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Heterosynaptic interactions between dorsal and ventral hippocampus in individual medium spiny neurons of the nucleus accumbens ventromedial shell.bioRxiv : the preprint server for biology · 2025Article
- Ethanol self-administration targets GluA2-containing AMPA receptor expression and synaptic activity in the nucleus accumbens in a manner that drives the positive reinforcing properties of the drug.Psychopharmacology · 2025Article
- Neurobiology of the incubation of drug craving: An update.Pharmacological reviews · 2025Review
- Epac2-mediated synaptic insertion of CaNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Dissociating the incubation of appetitive and consummatory behavior in a model of oral cocaine self-administration.bioRxiv : the preprint server for biology · 2025Article
- Synaptic Plasticity Linked to Ionotropic Glutamate Receptors After Nicotine Exposure.Current neuropharmacology · 2025Review
- Targeting Neuroplasticity in Substance Use Disorders: Implications for Therapeutics.Annual review of pharmacology and toxicology · 2025Review
- Retinoic acid-mediated homeostatic plasticity in the nucleus accumbens core contributes to incubation of cocaine craving.Psychopharmacology · 2024Article
- Sex-Specific Mechanisms Underlie Long-Term Potentiation at Hippocampus→Medium Spiny Neuron Synapses in the Medial Shell of the Nucleus Accumbens.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Effects of junk-food on food-motivated behavior and nucleus accumbens glutamate plasticity; insights into the mechanism of calcium-permeable AMPA receptor recruitment.Neuropharmacology · 2024Article
- Oxycodone withdrawal is associated with increased cocaine self-administration and aberrant accumbens glutamate plasticity in rats.Neuropharmacology · 2024Article
90 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
In animal models of drug addiction, cocaine exposure has been shown to increase levels of calcium-permeable AMPA receptors (CP-AMPARs) in two brain regions that are critical for motivation and reward-the ventral tegmental area (VTA) and the nucleus accumbens (NAc). This review compares CP-AMPAR plasticity in the two brain regions and addresses its functional significance. In VTA dopamine neurons, cocaine exposure results in synaptic insertion of high conductance CP-AMPARs in exchange for lower conductance calcium-impermeable AMPARs (CI-AMPARs). This plasticity is rapid in onset (hours), GluA2-dependent, and can be observed with a single cocaine injection. Whereas it is short-lived after experimenter-administered cocaine, it persists for months after cocaine self-administration. In addition to strengthening synapses and altering Ca(2+) signaling, CP-AMPAR insertion alters subsequent induction of plasticity at VTA synapses. However, CP-AMPAR insertion is unlikely to mediate the increased DA cell activity that occurs during early withdrawal from cocaine exposure. Metabotropic glutamate receptor 1 (mGluR1) exerts a negative influence on CP-AMPAR accumulation in the VTA. Acutely, mGluR1 stimulation elicits a form of LTD resulting from CP-AMPAR removal and CI-AMPAR insertion. In medium spiny neurons (MSNs) of the NAc, extended access cocaine self-administration is required to increase CP-AMPAR levels. This is first detected after approximately a month of withdrawal and then persists. Once present in NAc synapses, CP-AMPARs mediate the expression of incubation of cue-induced cocaine craving. The mechanism of their accumulation may be GluA1-dependent, which differs from that observed in the VTA. However, similar to VTA, mGluR1 stimulation removes CP-AMPARs from MSN synapses. Loss of mGluR1 tone during cocaine withdrawal may contribute to CP-AMPAR accumulation in the NAc. Thus, results in both brain regions point to the possibility of using positive modulators of mGluR1 as treatments for cocaine addiction.
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