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

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

Autor Abrahao, Karina Possa Autor UNIFESP Google Scholar
Ariwodola, Olusegun J. Google Scholar
Butler, Tracy R. Google Scholar
Rau, Andrew R. Google Scholar
Skelly, Mary Jane Google Scholar
Carter, Eugenia Google Scholar
Alexander, Nancy P. Google Scholar
McCool, Brian A. Google Scholar
Souza-Formigoni, Maria Lucia O. Autor UNIFESP Google Scholar
Weiner, Jeffrey L. Google Scholar
Instituição Wake Forest Sch Med
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Resumo 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.
Idioma Inglês
Financiador National Institutes of Health
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Associacao Fundo de Incentivo a Pesquisa (AFIP)
Número do financiamento National Institutes of Health: AA 21099
National Institutes of Health: AA 17531
National Institutes of Health: AA 10422
National Institutes of Health: AA 14445
CAPES: 0321-10-9
FAPESP: 2008/01819-5
Data de publicação 2013-03-13
Publicado em Journal of Neuroscience. Washington: Soc Neuroscience, v. 33, n. 11, p. 4834-4842, 2013.
ISSN 0270-6474 (Sherpa/Romeo, fator de impacto)
Publicador Soc Neuroscience
Extensão 4834-4842
Fonte http://dx.doi.org/10.1523/JNEUROSCI.5839-11.2013
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000316119200018
Endereço permanente http://repositorio.unifesp.br/handle/11600/36085

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