Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABAB1 knockout mice

Autores
Varani, Andrés Pablo; Machado Moutinho, Lirane; Bettler, Bernhard; Balerio, Graciela Noemí
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Nicotine is the main active component of tobacco, and has both acute and chronic pharmacological effects that can contribute to its abuse potential in humans. The aim of the present study was to evaluate a possible role of GABAB receptors in acute and chronic responses to nicotine administration, by comparing GABAB1 knockout mice and their wild-type littermates. In wild-type mice, acute nicotine administration (0.5, 1, 3 and 6 mg/kg, sc) dose-dependently decreased locomotor activity, and induced antinociceptive responses in the tail-immersion and hot-plate tests. In GABAB1 knockout mice, the hypolocomotive effect was observed only with the highest dose of nicotine, and the antinociceptive responses in both tests were significantly reduced in GABAB1 knockout mice compared to their wild-type littermate. Additionally, nicotine elicited anxiolytic- (0.05 mg/kg) and anxiogenic-like (0.8 mg/kg) responses in the elevated plus-maze test in wild-type mice, while selectively the anxiolytic-like effect was abolished in GABAB1 knockout mice. We further investigated nicotine withdrawal in mice chronically treated with nicotine (25 mg/kg/day, sc). Mecamylamine (1 mg/kg, sc) precipitated several somatic signs of nicotine withdrawal in wild-type mice. However, signs of nicotine withdrawal were missing in GABA B1 knockout mice. Finally, there was a decreased immunoreactivity of Fos-positive nuclei in the bed nucleus of the stria terminalis, basolateral amygdaloid nucleus and hippocampal dentate gyrus in abstinent wild-type but not in GABAB1 knockout mice. These results reveal an interaction between the GABAB system and the neurochemical systems through which nicotine exerts its acute and long-term effects. © 2012 Elsevier Ltd. All rights reserved.
Fil: Varani, Andrés Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Machado Moutinho, Lirane. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Bettler, Bernhard. Universidad de Basilea; Suiza
Fil: Balerio, Graciela Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina
Materia
Anxiety-Like Behaviour
C-Fos
Gabab Receptor
Nicotine
Nociception
Withdrawal
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/67384
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/67384
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABAB1 knockout miceVarani, Andrés PabloMachado Moutinho, LiraneBettler, BernhardBalerio, Graciela NoemíAnxiety-Like BehaviourC-FosGabab ReceptorNicotineNociceptionWithdrawalhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Nicotine is the main active component of tobacco, and has both acute and chronic pharmacological effects that can contribute to its abuse potential in humans. The aim of the present study was to evaluate a possible role of GABAB receptors in acute and chronic responses to nicotine administration, by comparing GABAB1 knockout mice and their wild-type littermates. In wild-type mice, acute nicotine administration (0.5, 1, 3 and 6 mg/kg, sc) dose-dependently decreased locomotor activity, and induced antinociceptive responses in the tail-immersion and hot-plate tests. In GABAB1 knockout mice, the hypolocomotive effect was observed only with the highest dose of nicotine, and the antinociceptive responses in both tests were significantly reduced in GABAB1 knockout mice compared to their wild-type littermate. Additionally, nicotine elicited anxiolytic- (0.05 mg/kg) and anxiogenic-like (0.8 mg/kg) responses in the elevated plus-maze test in wild-type mice, while selectively the anxiolytic-like effect was abolished in GABAB1 knockout mice. We further investigated nicotine withdrawal in mice chronically treated with nicotine (25 mg/kg/day, sc). Mecamylamine (1 mg/kg, sc) precipitated several somatic signs of nicotine withdrawal in wild-type mice. However, signs of nicotine withdrawal were missing in GABA B1 knockout mice. Finally, there was a decreased immunoreactivity of Fos-positive nuclei in the bed nucleus of the stria terminalis, basolateral amygdaloid nucleus and hippocampal dentate gyrus in abstinent wild-type but not in GABAB1 knockout mice. These results reveal an interaction between the GABAB system and the neurochemical systems through which nicotine exerts its acute and long-term effects. © 2012 Elsevier Ltd. All rights reserved.Fil: Varani, Andrés Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Machado Moutinho, Lirane. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Bettler, Bernhard. Universidad de Basilea; SuizaFil: Balerio, Graciela Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; ArgentinaPergamon-Elsevier Science Ltd2012-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/67384Varani, Andrés Pablo; Machado Moutinho, Lirane; Bettler, Bernhard; Balerio, Graciela Noemí; Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABAB1 knockout mice; Pergamon-Elsevier Science Ltd; Neuropharmacology; 63; 5; 10-2012; 863-8720028-3908CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.neuropharm.2012.06.006info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S002839081200264Xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:11:07Zoai:ri.conicet.gov.ar:11336/67384instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:11:07.885CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABAB1 knockout mice
title Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABAB1 knockout mice
spellingShingle Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABAB1 knockout mice
Varani, Andrés Pablo
Anxiety-Like Behaviour
C-Fos
Gabab Receptor
Nicotine
Nociception
Withdrawal
title_short Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABAB1 knockout mice
title_full Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABAB1 knockout mice
title_fullStr Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABAB1 knockout mice
title_full_unstemmed Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABAB1 knockout mice
title_sort Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABAB1 knockout mice
dc.creator.none.fl_str_mv Varani, Andrés Pablo
Machado Moutinho, Lirane
Bettler, Bernhard
Balerio, Graciela Noemí
author Varani, Andrés Pablo
author_facet Varani, Andrés Pablo
Machado Moutinho, Lirane
Bettler, Bernhard
Balerio, Graciela Noemí
author_role author
author2 Machado Moutinho, Lirane
Bettler, Bernhard
Balerio, Graciela Noemí
author2_role author
author
author
dc.subject.none.fl_str_mv Anxiety-Like Behaviour
C-Fos
Gabab Receptor
Nicotine
Nociception
Withdrawal
topic Anxiety-Like Behaviour
C-Fos
Gabab Receptor
Nicotine
Nociception
Withdrawal
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Nicotine is the main active component of tobacco, and has both acute and chronic pharmacological effects that can contribute to its abuse potential in humans. The aim of the present study was to evaluate a possible role of GABAB receptors in acute and chronic responses to nicotine administration, by comparing GABAB1 knockout mice and their wild-type littermates. In wild-type mice, acute nicotine administration (0.5, 1, 3 and 6 mg/kg, sc) dose-dependently decreased locomotor activity, and induced antinociceptive responses in the tail-immersion and hot-plate tests. In GABAB1 knockout mice, the hypolocomotive effect was observed only with the highest dose of nicotine, and the antinociceptive responses in both tests were significantly reduced in GABAB1 knockout mice compared to their wild-type littermate. Additionally, nicotine elicited anxiolytic- (0.05 mg/kg) and anxiogenic-like (0.8 mg/kg) responses in the elevated plus-maze test in wild-type mice, while selectively the anxiolytic-like effect was abolished in GABAB1 knockout mice. We further investigated nicotine withdrawal in mice chronically treated with nicotine (25 mg/kg/day, sc). Mecamylamine (1 mg/kg, sc) precipitated several somatic signs of nicotine withdrawal in wild-type mice. However, signs of nicotine withdrawal were missing in GABA B1 knockout mice. Finally, there was a decreased immunoreactivity of Fos-positive nuclei in the bed nucleus of the stria terminalis, basolateral amygdaloid nucleus and hippocampal dentate gyrus in abstinent wild-type but not in GABAB1 knockout mice. These results reveal an interaction between the GABAB system and the neurochemical systems through which nicotine exerts its acute and long-term effects. © 2012 Elsevier Ltd. All rights reserved.
Fil: Varani, Andrés Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Machado Moutinho, Lirane. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Bettler, Bernhard. Universidad de Basilea; Suiza
Fil: Balerio, Graciela Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina
description Nicotine is the main active component of tobacco, and has both acute and chronic pharmacological effects that can contribute to its abuse potential in humans. The aim of the present study was to evaluate a possible role of GABAB receptors in acute and chronic responses to nicotine administration, by comparing GABAB1 knockout mice and their wild-type littermates. In wild-type mice, acute nicotine administration (0.5, 1, 3 and 6 mg/kg, sc) dose-dependently decreased locomotor activity, and induced antinociceptive responses in the tail-immersion and hot-plate tests. In GABAB1 knockout mice, the hypolocomotive effect was observed only with the highest dose of nicotine, and the antinociceptive responses in both tests were significantly reduced in GABAB1 knockout mice compared to their wild-type littermate. Additionally, nicotine elicited anxiolytic- (0.05 mg/kg) and anxiogenic-like (0.8 mg/kg) responses in the elevated plus-maze test in wild-type mice, while selectively the anxiolytic-like effect was abolished in GABAB1 knockout mice. We further investigated nicotine withdrawal in mice chronically treated with nicotine (25 mg/kg/day, sc). Mecamylamine (1 mg/kg, sc) precipitated several somatic signs of nicotine withdrawal in wild-type mice. However, signs of nicotine withdrawal were missing in GABA B1 knockout mice. Finally, there was a decreased immunoreactivity of Fos-positive nuclei in the bed nucleus of the stria terminalis, basolateral amygdaloid nucleus and hippocampal dentate gyrus in abstinent wild-type but not in GABAB1 knockout mice. These results reveal an interaction between the GABAB system and the neurochemical systems through which nicotine exerts its acute and long-term effects. © 2012 Elsevier Ltd. All rights reserved.
publishDate 2012
dc.date.none.fl_str_mv 2012-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/67384
Varani, Andrés Pablo; Machado Moutinho, Lirane; Bettler, Bernhard; Balerio, Graciela Noemí; Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABAB1 knockout mice; Pergamon-Elsevier Science Ltd; Neuropharmacology; 63; 5; 10-2012; 863-872
0028-3908
CONICET Digital
CONICET
url http://hdl.handle.net/11336/67384
identifier_str_mv Varani, Andrés Pablo; Machado Moutinho, Lirane; Bettler, Bernhard; Balerio, Graciela Noemí; Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABAB1 knockout mice; Pergamon-Elsevier Science Ltd; Neuropharmacology; 63; 5; 10-2012; 863-872
0028-3908
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neuropharm.2012.06.006
info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S002839081200264X
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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