ArticleSynapse (New York, N.Y.)2011
Repeated cocaine exposure decreases dopamine D₂-like receptor modulation of Ca(2+) homeostasis in rat nucleus accumbens neurons.
Article in Synapse (New York, N.Y.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 38 citations in OpenAlex.
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- Immunosuppressant treatment reduces cocaine-induced behavioral sensitization in mice.Frontiers in pharmacology · 2026Article
- Dopamine receptors and organ fibrosis.Biochemistry and biophysics reports · 2025Review
- Cocaine's effects on the reactivity of the medial prefrontal cortex to ventral tegmental area stimulation: optical imaging study in mice.Addiction (Abingdon, England) · 2022Article
- Psychoanalytical Considerations of Emotion Regulation Disorders in Multiple Complex-Traumatized Children-A Study Protocol of the Prospective Study MuKi.Frontiers in human neuroscience · 2022Article
- The Vasomotor Response to Dopamine Is Altered in the Rat Model of l-dopa-Induced Dyskinesia.Movement disorders : official journal of the Movement Disorder Society · 2021Article
- Cocaine addicted rats show reduced neural activity as revealed by manganese-enhanced MRI.Scientific reports · 2020Article
- Interaction Between the Trace Amine-Associated Receptor 1 and the Dopamine DScientific reports · 2017Article
- Differential alterations of intracellular [CaTranslational brain rhythmicity · 2017Article
- Dopamine elevates and lowers astroglial CaGlia · 2017Article
- Emerging pathways driving early synaptic pathology in Alzheimer's disease.Biochemical and biophysical research communications · 2017Review
- Self-directed exploration provides a Ncs1-dependent learning bonus.Scientific reports · 2015Article
- Repeated cocaine treatment enhances HIV-1 Tat-induced cortical excitability via over-activation of L-type calcium channels.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2014Article
- Nucleus accumbens neuronal activity correlates to the animal's behavioral response to acute and chronic methylphenidate.Physiology & behavior · 2014Article
- Chronic cocaine dampens dopamine signaling during cocaine intoxication and unbalances D1 over D2 receptor signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction.Psychopharmacology · 2012Review
- Addiction circuitry in the human brain.Annual review of pharmacology and toxicology · 2012Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The nucleus accumbens (NAc) is a limbic structure in the forebrain that plays a critical role in cognitive function and addiction. Dopamine modulates activity of medium spiny neurons (MSNs) in the NAc. Both dopamine D₁-like and D₂-like receptors (including D1R or D(1,5)R and D2R or D(2,3,4)R, respectively) are thought to play critical roles in cocaine addiction. Our previous studies demonstrated that repeated cocaine exposure (which alters dopamine transmission) decreases excitability of NAc MSNs in cocaine-sensitized, withdrawn rats. This decrease is characterized by a reduction in voltage-sensitive Na(+) currents and high voltage-activated Ca(2+) currents, along with increased voltage-gated K(+) currents. These changes are associated with enhanced activity in the D1R/cAMP/PKA/protein phosphatase 1 pathway and diminished calcineurin function. Although D1R-mediated signaling is enhanced by repeated cocaine exposure, little is known whether and how the D2R is implicated in the cocaine-induced NAc dysfunction. Here, we performed a combined electrophysiological, biochemical, and neuroimaging study that reveals the cocaine-induced dysregulation of Ca(2+) homeostasis with involvement of D2R. Our novel findings reveal that D2R stimulation reduced Ca(2+) influx preferentially via the L-type Ca(2+) channels and evoked intracellular Ca(2+) release, likely via inhibiting the cAMP/PKA cascade, in the NAc MSNs of drug-free rats. However, repeated cocaine exposure abolished the D₂R effects on modulating Ca(2+) homeostasis with enhanced PKA activity and led to a decrease in whole-cell Ca(2+) influx. These adaptations, which persisted for 21 days during cocaine abstinence, may contribute to the mechanism of cocaine withdrawal.
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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.