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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Locomotor Sensitization to Ethanol Impairs NMDA Receptor-Dependent Synaptic Plasticity in the Nucleus Accumbens and Increases Ethanol Self-Administration

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Abrahao, Karina Possa [1, 2] ; Ariwodola, Olusegun J. [2] ; Butler, Tracy R. [2] ; Rau, Andrew R. [2] ; Skelly, Mary Jane [2] ; Carter, Eugenia [2] ; Alexander, Nancy P. [2] ; McCool, Brian A. [2] ; Souza-Formigoni, Maria Lucia O. [3] ; Weiner, Jeffrey L. [2]
Total Authors: 10
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Farmacol, BR-05508900 Sao Paulo - Brazil
[2] Wake Forest Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 - USA
[3] Univ Fed Sao Paulo, Dept Psicobiol, Escola Paulista Med, BR-04023062 Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: JOURNAL OF NEUROSCIENCE; v. 33, n. 11, p. 4834-4842, MAR 13 2013.
Web of Science Citations: 48

Although alcoholism is a worldwide problem resulting in millions of deaths, only a small percentage of alcohol users become addicted. The specific neural substrates responsible for individual differences in vulnerability to alcohol addiction are not known. In this study, we used rodent models to study behavioral and synaptic correlates related to individual differences in the development of ethanol locomotor sensitization, a form of drug-dependent behavioral plasticity associated with addiction vulnerability. Male Swiss Webster mice were treated daily with saline or 1.8 g/kg ethanol for 21 d. Locomotor activity tests were performed once a week for 15 min immediately after saline or ethanol injections. After at least 11 d of withdrawal, cohorts of saline-or ethanol-treated mice were used to characterize the relationships between locomotor sensitization, ethanol drinking, and glutamatergic synaptic transmission in the nucleus accumbens. Ethanol-treated mice that expressed locomotor sensitization to ethanol drank significantly more ethanol than saline-treated subjects and ethanol-treated animals resilient to this form of behavioral plasticity. Moreover, ethanol-sensitized mice also had reduced accumbal NMDA receptor function and expression, as well as deficits in NMDA receptor-dependent long-term depression in the nucleus accumbens core after a protracted withdrawal. These findings suggest that disruption of accumbal core NMDA receptor-dependent plasticity may represent a synaptic correlate associated with ethanol-induced locomotor sensitization and increased propensity to consume ethanol. (AU)

FAPESP's process: 08/01819-5 - Role of D1, NMDA receptors and DARPP-32 protein of nucleus accumbens in the expression of behavioral sensitization to ethanol
Grantee:Karina Possa Abrahão
Support type: Scholarships in Brazil - Doctorate