Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum

Growing awareness of cerebellar involvement in addiction is based on the cerebellum's intermediary position between motor and reward, potentially acting as an interface between motivational and cognitive functions. Here, we examined the impact of acute and repeated cocaine exposure on the two m...

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Autores: Palomino, Ana, Pavón, Francisco Javier, Blanco Calvo, Eduardo, Serrano, Antonia, Arrabal, Sergio, Rivera, Patricia, Alén, Francisco, Vargas, Antonio, Bilbao, Ainhoa, Rubio, Leticia, Rodríguez de Fonseca, Fernando, Suárez, Juan
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Recursos:Universitat de Lleida (UdL)
Repositorio:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/47966
Acesso em linha:https://doi.org/10.3389/fnint.2014.00022
http://hdl.handle.net/10459.1/47966
Access Level:acceso abierto
Palavra-chave:Cocaine
Sensitization
Cannabinoid
Glutamate
Tyrosine hydroxylase
Mouse
Cerebellum
Cocaïna
Cervell
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repository_id_str
spelling Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellumPalomino, AnaPavón, Francisco JavierBlanco Calvo, EduardoSerrano, AntoniaArrabal, SergioRivera, PatriciaAlén, FranciscoVargas, AntonioBilbao, AinhoaRubio, LeticiaRodríguez de Fonseca, FernandoSuárez, JuanCocaineSensitizationCannabinoidGlutamateTyrosine hydroxylaseMouseCerebellumCocaïnaCervellGrowing awareness of cerebellar involvement in addiction is based on the cerebellum's intermediary position between motor and reward, potentially acting as an interface between motivational and cognitive functions. Here, we examined the impact of acute and repeated cocaine exposure on the two main signaling systems in the mouse cerebellum: the endocannabinoid (eCB) and glutamate systems. To this end, we investigated whether eCB signaling-related gene and protein expression {cannabinoid receptor type 1 receptors and enzymes that produce [diacylglycerol lipase alpha/beta (DAGLα/β) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD)] and degrade [monoacylglycerol lipase (MAGL) and fatty acid amino hydrolase (FAAH)] eCB} were altered. In addition, we analyzed the gene expression of relevant components of the glutamate signaling system [glutamate synthesizing enzymes liver-type glutaminase isoform (LGA) and kidney-type glutaminase isoform (KGA), metabotropic glutamatergic receptor (mGluR3/5), NMDA-ionotropic glutamatergic receptor (NR1/2A/2B/2C) and AMPA-ionotropic receptor subunits (GluR1/2/3/4)] and the gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, because noradrenergic terminals innervate the cerebellar cortex. Results indicated that acute cocaine exposure decreased DAGLα expression, suggesting a down-regulation of 2-arachidonylglycerol (2-AG) production, as well as gene expression of TH, KGA, mGluR3 and all ionotropic receptor subunits analyzed in the cerebellum. The acquisition of conditioned locomotion and sensitization after repeated cocaine exposure were associated with an increased NAPE-PLD/FAAH ratio, suggesting enhanced anandamide production, and a decreased DAGLβ/MAGL ratio, suggesting decreased 2-AG generation. Repeated cocaine also increased LGA gene expression but had no effect on glutamate receptors. These findings indicate that acute cocaine modulates the expression of the eCB and glutamate systems. Repeated cocaine results in normalization of glutamate receptor expression, although sustained changes in eCB is observed. We suggest that cocaine-induced alterations to cerebellar eCB should be considered when analyzing the adaptations imposed by psychostimulants that lead to addiction.Frontiers Media S.A.2014info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://doi.org/10.3389/fnint.2014.00022http://hdl.handle.net/10459.1/47966reponame:Repositori Obert UdL instname:Universitat de Lleida (UdL)InglésReproducció del document publicat a https://doi.org/10.3389/fnint.2014.00022Frontiers in integrative neuroscience, 2014, vol. 8, num. 22, p. 1-12cc-by (c) els autors, 2014info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/es/deed.caoai:repositori.udl.cat:10459.1/479662026-06-24T12:42:17Z
dc.title.none.fl_str_mv Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum
title Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum
spellingShingle Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum
Palomino, Ana
Cocaine
Sensitization
Cannabinoid
Glutamate
Tyrosine hydroxylase
Mouse
Cerebellum
Cocaïna
Cervell
title_short Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum
title_full Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum
title_fullStr Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum
title_full_unstemmed Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum
title_sort Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum
dc.creator.none.fl_str_mv Palomino, Ana
Pavón, Francisco Javier
Blanco Calvo, Eduardo
Serrano, Antonia
Arrabal, Sergio
Rivera, Patricia
Alén, Francisco
Vargas, Antonio
Bilbao, Ainhoa
Rubio, Leticia
Rodríguez de Fonseca, Fernando
Suárez, Juan
author Palomino, Ana
author_facet Palomino, Ana
Pavón, Francisco Javier
Blanco Calvo, Eduardo
Serrano, Antonia
Arrabal, Sergio
Rivera, Patricia
Alén, Francisco
Vargas, Antonio
Bilbao, Ainhoa
Rubio, Leticia
Rodríguez de Fonseca, Fernando
Suárez, Juan
author_role author
author2 Pavón, Francisco Javier
Blanco Calvo, Eduardo
Serrano, Antonia
Arrabal, Sergio
Rivera, Patricia
Alén, Francisco
Vargas, Antonio
Bilbao, Ainhoa
Rubio, Leticia
Rodríguez de Fonseca, Fernando
Suárez, Juan
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cocaine
Sensitization
Cannabinoid
Glutamate
Tyrosine hydroxylase
Mouse
Cerebellum
Cocaïna
Cervell
topic Cocaine
Sensitization
Cannabinoid
Glutamate
Tyrosine hydroxylase
Mouse
Cerebellum
Cocaïna
Cervell
description Growing awareness of cerebellar involvement in addiction is based on the cerebellum's intermediary position between motor and reward, potentially acting as an interface between motivational and cognitive functions. Here, we examined the impact of acute and repeated cocaine exposure on the two main signaling systems in the mouse cerebellum: the endocannabinoid (eCB) and glutamate systems. To this end, we investigated whether eCB signaling-related gene and protein expression {cannabinoid receptor type 1 receptors and enzymes that produce [diacylglycerol lipase alpha/beta (DAGLα/β) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD)] and degrade [monoacylglycerol lipase (MAGL) and fatty acid amino hydrolase (FAAH)] eCB} were altered. In addition, we analyzed the gene expression of relevant components of the glutamate signaling system [glutamate synthesizing enzymes liver-type glutaminase isoform (LGA) and kidney-type glutaminase isoform (KGA), metabotropic glutamatergic receptor (mGluR3/5), NMDA-ionotropic glutamatergic receptor (NR1/2A/2B/2C) and AMPA-ionotropic receptor subunits (GluR1/2/3/4)] and the gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, because noradrenergic terminals innervate the cerebellar cortex. Results indicated that acute cocaine exposure decreased DAGLα expression, suggesting a down-regulation of 2-arachidonylglycerol (2-AG) production, as well as gene expression of TH, KGA, mGluR3 and all ionotropic receptor subunits analyzed in the cerebellum. The acquisition of conditioned locomotion and sensitization after repeated cocaine exposure were associated with an increased NAPE-PLD/FAAH ratio, suggesting enhanced anandamide production, and a decreased DAGLβ/MAGL ratio, suggesting decreased 2-AG generation. Repeated cocaine also increased LGA gene expression but had no effect on glutamate receptors. These findings indicate that acute cocaine modulates the expression of the eCB and glutamate systems. Repeated cocaine results in normalization of glutamate receptor expression, although sustained changes in eCB is observed. We suggest that cocaine-induced alterations to cerebellar eCB should be considered when analyzing the adaptations imposed by psychostimulants that lead to addiction.
publishDate 2014
dc.date.none.fl_str_mv 2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.3389/fnint.2014.00022
http://hdl.handle.net/10459.1/47966
url https://doi.org/10.3389/fnint.2014.00022
http://hdl.handle.net/10459.1/47966
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a https://doi.org/10.3389/fnint.2014.00022
Frontiers in integrative neuroscience, 2014, vol. 8, num. 22, p. 1-12
dc.rights.none.fl_str_mv cc-by (c) els autors, 2014
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/deed.ca
rights_invalid_str_mv cc-by (c) els autors, 2014
http://creativecommons.org/licenses/by/3.0/es/deed.ca
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
dc.source.none.fl_str_mv reponame:Repositori Obert UdL
instname:Universitat de Lleida (UdL)
instname_str Universitat de Lleida (UdL)
reponame_str Repositori Obert UdL
collection Repositori Obert UdL
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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