Individual Differences in Ethanol Locomotor Sensitization Are Associated with Dopamine D1 Receptor Intra-Cellular Signaling of DARPP-32 in the Nucleus Accumbens
Autor(a) principal: | |
---|---|
Data de Publicação: | 2014 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/37871 http://dx.doi.org/10.1371/journal.pone.0098296 |
Resumo: | In mice there are clear individual differences in the development of behavioral sensitization to ethanol, a progressive potentiation of its psychomotor stimulant effect. Variability in the behavioral responses to ethanol has been associated with alcohol preference. Here we investigated if the functional hyperresponsiveness of D1 receptors observed in ethanol sensitized mice leads to an increased activation of DARPP-32, a central regulatory protein in medium spiny neurons, in the nucleus accumbens - a brain region known to play a role in drug reinforcement. Swiss Webster mice received ethanol (2.2 g/kg/day) or saline i.p. administrations for 21 days and were weekly evaluated regarding their locomotor activity. From those treated with ethanol, the 33% with the highest levels of locomotor activity were classified as sensitized'' and the 33% with the lowest levels as non-sensitized''. the latter presented similar locomotor levels to those of saline-treated mice. Different subgroups of mice received intra-accumbens administrations of saline and, 48 h later, SKF-38393, D1 receptor agonist 0.1 or 1 mg/side. Indeed, sensitized mice presented functional hyperresponsiveness of D1 receptors in the accumbens. Two weeks following the ethanol treatment, other subgroups received systemic saline or SKF 10 mg/kg, 20 min before the euthanasia. the nucleus accumbens were dissected for the Western Blot analyses of total DARPP-32 and phospho-Thr34-DARPP-32 expression. D1 receptor activation induced higher phospho-Thr34-DARPP-32 expression in sensitized mice than in non-sensitized or saline. the functionally hyperresponsiveness of D1 receptors in the nucleus accumbens is associated with an increased phospho-Thr34-DARPP-32 expression after D1 receptor activation. These data suggest that an enduring increase in the sensitivity of the dopamine D1 receptor intracellular pathway sensitivity represents a neurobiological correlate associated with the development of locomotor sensitization to ethanol. |
id |
UFSP_8f22e75667ee45a36f95d49505a6f6a8 |
---|---|
oai_identifier_str |
oai:repositorio.unifesp.br:11600/37871 |
network_acronym_str |
UFSP |
network_name_str |
Repositório Institucional da UNIFESP |
repository_id_str |
3465 |
spelling |
Abrahao, Karina Possa [UNIFESP]Goeldner, Francine Oliveira [UNIFESP]Oliveira Souza-Formigoni, Maria Lucia [UNIFESP]Universidade Federal de São Paulo (UNIFESP)2016-01-24T14:37:27Z2016-01-24T14:37:27Z2014-06-11Plos One. San Francisco: Public Library Science, v. 9, n. 6, 9 p., 2014.1932-6203http://repositorio.unifesp.br/handle/11600/37871http://dx.doi.org/10.1371/journal.pone.0098296WOS000338631000015.pdf10.1371/journal.pone.0098296WOS:000338631000015In mice there are clear individual differences in the development of behavioral sensitization to ethanol, a progressive potentiation of its psychomotor stimulant effect. Variability in the behavioral responses to ethanol has been associated with alcohol preference. Here we investigated if the functional hyperresponsiveness of D1 receptors observed in ethanol sensitized mice leads to an increased activation of DARPP-32, a central regulatory protein in medium spiny neurons, in the nucleus accumbens - a brain region known to play a role in drug reinforcement. Swiss Webster mice received ethanol (2.2 g/kg/day) or saline i.p. administrations for 21 days and were weekly evaluated regarding their locomotor activity. From those treated with ethanol, the 33% with the highest levels of locomotor activity were classified as sensitized'' and the 33% with the lowest levels as non-sensitized''. the latter presented similar locomotor levels to those of saline-treated mice. Different subgroups of mice received intra-accumbens administrations of saline and, 48 h later, SKF-38393, D1 receptor agonist 0.1 or 1 mg/side. Indeed, sensitized mice presented functional hyperresponsiveness of D1 receptors in the accumbens. Two weeks following the ethanol treatment, other subgroups received systemic saline or SKF 10 mg/kg, 20 min before the euthanasia. the nucleus accumbens were dissected for the Western Blot analyses of total DARPP-32 and phospho-Thr34-DARPP-32 expression. D1 receptor activation induced higher phospho-Thr34-DARPP-32 expression in sensitized mice than in non-sensitized or saline. the functionally hyperresponsiveness of D1 receptors in the nucleus accumbens is associated with an increased phospho-Thr34-DARPP-32 expression after D1 receptor activation. These data suggest that an enduring increase in the sensitivity of the dopamine D1 receptor intracellular pathway sensitivity represents a neurobiological correlate associated with the development of locomotor sensitization to ethanol.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Associacao Fundo Incentivo a Pesquisa (AFIP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Escola Paulista Med, Dept Psicobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Psicobiol, São Paulo, BrazilFAPESP: 2008/01819-5Web of Science9engPublic Library SciencePlos OneIndividual Differences in Ethanol Locomotor Sensitization Are Associated with Dopamine D1 Receptor Intra-Cellular Signaling of DARPP-32 in the Nucleus Accumbensinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000338631000015.pdfapplication/pdf935523${dspace.ui.url}/bitstream/11600/37871/1/WOS000338631000015.pdf9cb85f7a9a325df7c8df75640b6271bfMD51open accessTEXTWOS000338631000015.pdf.txtWOS000338631000015.pdf.txtExtracted texttext/plain43262${dspace.ui.url}/bitstream/11600/37871/2/WOS000338631000015.pdf.txtea5bd82d3806e457c1185ff09fa47d15MD52open access11600/378712022-07-08 10:45:12.152open accessoai:repositorio.unifesp.br:11600/37871Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-07-08T13:45:12Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Individual Differences in Ethanol Locomotor Sensitization Are Associated with Dopamine D1 Receptor Intra-Cellular Signaling of DARPP-32 in the Nucleus Accumbens |
title |
Individual Differences in Ethanol Locomotor Sensitization Are Associated with Dopamine D1 Receptor Intra-Cellular Signaling of DARPP-32 in the Nucleus Accumbens |
spellingShingle |
Individual Differences in Ethanol Locomotor Sensitization Are Associated with Dopamine D1 Receptor Intra-Cellular Signaling of DARPP-32 in the Nucleus Accumbens Abrahao, Karina Possa [UNIFESP] |
title_short |
Individual Differences in Ethanol Locomotor Sensitization Are Associated with Dopamine D1 Receptor Intra-Cellular Signaling of DARPP-32 in the Nucleus Accumbens |
title_full |
Individual Differences in Ethanol Locomotor Sensitization Are Associated with Dopamine D1 Receptor Intra-Cellular Signaling of DARPP-32 in the Nucleus Accumbens |
title_fullStr |
Individual Differences in Ethanol Locomotor Sensitization Are Associated with Dopamine D1 Receptor Intra-Cellular Signaling of DARPP-32 in the Nucleus Accumbens |
title_full_unstemmed |
Individual Differences in Ethanol Locomotor Sensitization Are Associated with Dopamine D1 Receptor Intra-Cellular Signaling of DARPP-32 in the Nucleus Accumbens |
title_sort |
Individual Differences in Ethanol Locomotor Sensitization Are Associated with Dopamine D1 Receptor Intra-Cellular Signaling of DARPP-32 in the Nucleus Accumbens |
author |
Abrahao, Karina Possa [UNIFESP] |
author_facet |
Abrahao, Karina Possa [UNIFESP] Goeldner, Francine Oliveira [UNIFESP] Oliveira Souza-Formigoni, Maria Lucia [UNIFESP] |
author_role |
author |
author2 |
Goeldner, Francine Oliveira [UNIFESP] Oliveira Souza-Formigoni, Maria Lucia [UNIFESP] |
author2_role |
author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Abrahao, Karina Possa [UNIFESP] Goeldner, Francine Oliveira [UNIFESP] Oliveira Souza-Formigoni, Maria Lucia [UNIFESP] |
description |
In mice there are clear individual differences in the development of behavioral sensitization to ethanol, a progressive potentiation of its psychomotor stimulant effect. Variability in the behavioral responses to ethanol has been associated with alcohol preference. Here we investigated if the functional hyperresponsiveness of D1 receptors observed in ethanol sensitized mice leads to an increased activation of DARPP-32, a central regulatory protein in medium spiny neurons, in the nucleus accumbens - a brain region known to play a role in drug reinforcement. Swiss Webster mice received ethanol (2.2 g/kg/day) or saline i.p. administrations for 21 days and were weekly evaluated regarding their locomotor activity. From those treated with ethanol, the 33% with the highest levels of locomotor activity were classified as sensitized'' and the 33% with the lowest levels as non-sensitized''. the latter presented similar locomotor levels to those of saline-treated mice. Different subgroups of mice received intra-accumbens administrations of saline and, 48 h later, SKF-38393, D1 receptor agonist 0.1 or 1 mg/side. Indeed, sensitized mice presented functional hyperresponsiveness of D1 receptors in the accumbens. Two weeks following the ethanol treatment, other subgroups received systemic saline or SKF 10 mg/kg, 20 min before the euthanasia. the nucleus accumbens were dissected for the Western Blot analyses of total DARPP-32 and phospho-Thr34-DARPP-32 expression. D1 receptor activation induced higher phospho-Thr34-DARPP-32 expression in sensitized mice than in non-sensitized or saline. the functionally hyperresponsiveness of D1 receptors in the nucleus accumbens is associated with an increased phospho-Thr34-DARPP-32 expression after D1 receptor activation. These data suggest that an enduring increase in the sensitivity of the dopamine D1 receptor intracellular pathway sensitivity represents a neurobiological correlate associated with the development of locomotor sensitization to ethanol. |
publishDate |
2014 |
dc.date.issued.fl_str_mv |
2014-06-11 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:37:27Z |
dc.date.available.fl_str_mv |
2016-01-24T14:37:27Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Plos One. San Francisco: Public Library Science, v. 9, n. 6, 9 p., 2014. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/37871 http://dx.doi.org/10.1371/journal.pone.0098296 |
dc.identifier.issn.none.fl_str_mv |
1932-6203 |
dc.identifier.file.none.fl_str_mv |
WOS000338631000015.pdf |
dc.identifier.doi.none.fl_str_mv |
10.1371/journal.pone.0098296 |
dc.identifier.wos.none.fl_str_mv |
WOS:000338631000015 |
identifier_str_mv |
Plos One. San Francisco: Public Library Science, v. 9, n. 6, 9 p., 2014. 1932-6203 WOS000338631000015.pdf 10.1371/journal.pone.0098296 WOS:000338631000015 |
url |
http://repositorio.unifesp.br/handle/11600/37871 http://dx.doi.org/10.1371/journal.pone.0098296 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Plos One |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
9 |
dc.publisher.none.fl_str_mv |
Public Library Science |
publisher.none.fl_str_mv |
Public Library Science |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
bitstream.url.fl_str_mv |
${dspace.ui.url}/bitstream/11600/37871/1/WOS000338631000015.pdf ${dspace.ui.url}/bitstream/11600/37871/2/WOS000338631000015.pdf.txt |
bitstream.checksum.fl_str_mv |
9cb85f7a9a325df7c8df75640b6271bf ea5bd82d3806e457c1185ff09fa47d15 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
_version_ |
1802764151396761600 |