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dc.contributor.author
Perez, Mariela Fernanda
dc.contributor.author
Ford, Kerstin A.
dc.contributor.author
Goussakov, Ivan
dc.contributor.author
Stutzmann, Grace E.
dc.contributor.author
Hu, Xiu-Ti
dc.date.available
2021-06-17T13:55:28Z
dc.date.issued
2011-02
dc.identifier.citation
Perez, Mariela Fernanda; Ford, Kerstin A.; Goussakov, Ivan; Stutzmann, Grace E.; Hu, Xiu-Ti; Repeated cocaine exposure decreases dopamine D2-like receptor modulation of Ca2+ homeostasis in rat nucleus accumbens neurons; Wiley-liss, div John Wiley & Sons Inc.; Synapse; 65; 2; 2-2011; 168-180
dc.identifier.issn
0887-4476
dc.identifier.uri
http://hdl.handle.net/11336/134074
dc.description.abstract
The nucleus accumbens is a limbic structure in the forebrain which plays a critical role in cognitive function and addiction. Dopamine modulates activity of medium spiny neurons in the nucleus accumbens. Both dopamine D1-like and D2-like receptors (including D1R or D1,5R, and D2R or D2,3,4R, 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alters dopamine transmission) decreases excitability of nucleus accumbens medium spiny neurons in cocaine-sensitized, withdrawn rats. This decrease is characterized by a reduction in voltage-sensitive Na+ currents and high voltage-activated Ca2+ 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. Though D1R-mediated signaling is enhanced by repeated cocaine exposure, little is known whether and how the D2R is implicated in the cocaine-induced nucleus accumbens dysfunction. Here, we performed a combined electrophysiological, biochemical, and neuroimaging study that reveals the cocaine-induced dysregulation of Ca2+ homeostasis with involvement of D2R. Our novel findings reveal that D2R stimulation reduced Ca2+ influx preferentially via the L-type Ca2+ channels and evoked intracellular Ca2+ release, likely via inhibiting the cAMP/PKA cascade, in the nucleus accumbens medium spiny neurons of drug-free rats. However, repeated cocaine exposure abolished the D2R effects on modulating Ca2+ homeostasis with enhanced PKA activity and led to a decrease in whole-cell Ca2+ influx. These adaptations, which persisted for 21 days during cocaine abstinence, may contribute to the mechanism of cocaine withdrawal.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Wiley-liss, div John Wiley & Sons Inc.
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Withdrawal,
dc.subject
L-type Ca2+ channel
dc.subject
PKA
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Patch clamp
dc.subject.classification
Neurociencias
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Repeated cocaine exposure decreases dopamine D2-like receptor modulation of Ca2+ homeostasis in rat nucleus accumbens neurons
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2021-04-23T17:22:56Z
dc.identifier.eissn
1098-2396
dc.journal.volume
65
dc.journal.number
2
dc.journal.pagination
168-180
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Perez, Mariela Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentina
dc.description.fil
Fil: Ford, Kerstin A.. Rosalind Franklin University of Medicine and Science; Estados Unidos
dc.description.fil
Fil: Goussakov, Ivan. Rosalind Franklin University of Medicine and Science; Estados Unidos
dc.description.fil
Fil: Stutzmann, Grace E.. Rosalind Franklin University of Medicine and Science; Estados Unidos
dc.description.fil
Fil: Hu, Xiu-Ti. Rush University Medical Center; Estados Unidos
dc.journal.title
Synapse
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3686293/
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1002%2Fsyn.20831
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1002/syn.20831
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