Mecamylamine-precipitated nicotine withdrawal syndrome and its prevention with baclofen: An autoradiographic study of α4β2 nicotinic acetylcholine receptors in mice

Autores
Varani, Andrés Pablo; Antonelli, Marta Cristina; Balerio, Graciela Noemí
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A previous study from our laboratory showed that baclofen (BAC, GABAB receptor agonist) was able to prevent the behavioral expression of nicotine (NIC) withdrawal syndrome. To further investigate the mechanisms underlying this effect, we conducted this study, with the aims of analyzing α4β2 nicotinic receptor density during NIC withdrawal and, in case we found any changes, of determining whether they could be prevented by pretreatment with BAC. Swiss Webster albino mice received NIC (2.5 mg/kg, s.c.) 4 times daily, for 7 days. On the 8th day, NIC-treated mice received the nicotinic antagonist mecamylamine (MEC; 2 mg/kg, i.p.) 1 h after the last dose of NIC. A second group of NIC-treated mice received BAC (2 mg/kg, i.p.) prior to MEC administration. Thirty minutes after MEC, mice were sacrificed and brain autoradiography with [3H]epibatidine was carried out at five different anatomical levels. Autoradiographic mapping showed a significant increase of α4β2 nicotinic receptor labeling during NIC withdrawal in the nucleus accumbens shell (AcbSh), medial habenular nucleus (HbM), thalamic nuclei, dorsal lateral geniculate (DLG) nucleus, fasciculus retroflexus (fr), ventral tegmental area, interpeduncular nucleus and superior colliculus. BAC pretreatment prevented the increased α4β2 nicotinic receptor binding sites in the AcbSh, MHb, thalamic nuclei, DLG nucleus and fr. The present results suggest a relationship between BAC´s preventive effect of the expression of NIC withdrawal signs, and its ability to restore the changes in α4β2 nicotinic receptor labeling, evidenced in specific brain areas in NIC withdrawn animals.
Fil: Varani, Andrés Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); Argentina
Fil: Antonelli, Marta Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencias "Profesor Eduardo de Robertis"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Balerio, Graciela Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina
Materia
[3h]Epibatidine
Baclofen
Nicotine
Α4β2 Nicotinic Receptor
Withdrawal
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/2827

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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Mecamylamine-precipitated nicotine withdrawal syndrome and its prevention with baclofen: An autoradiographic study of α4β2 nicotinic acetylcholine receptors in miceVarani, Andrés PabloAntonelli, Marta CristinaBalerio, Graciela Noemí[3h]EpibatidineBaclofenNicotineΑ4β2 Nicotinic ReceptorWithdrawalhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1A previous study from our laboratory showed that baclofen (BAC, GABAB receptor agonist) was able to prevent the behavioral expression of nicotine (NIC) withdrawal syndrome. To further investigate the mechanisms underlying this effect, we conducted this study, with the aims of analyzing α4β2 nicotinic receptor density during NIC withdrawal and, in case we found any changes, of determining whether they could be prevented by pretreatment with BAC. Swiss Webster albino mice received NIC (2.5 mg/kg, s.c.) 4 times daily, for 7 days. On the 8th day, NIC-treated mice received the nicotinic antagonist mecamylamine (MEC; 2 mg/kg, i.p.) 1 h after the last dose of NIC. A second group of NIC-treated mice received BAC (2 mg/kg, i.p.) prior to MEC administration. Thirty minutes after MEC, mice were sacrificed and brain autoradiography with [3H]epibatidine was carried out at five different anatomical levels. Autoradiographic mapping showed a significant increase of α4β2 nicotinic receptor labeling during NIC withdrawal in the nucleus accumbens shell (AcbSh), medial habenular nucleus (HbM), thalamic nuclei, dorsal lateral geniculate (DLG) nucleus, fasciculus retroflexus (fr), ventral tegmental area, interpeduncular nucleus and superior colliculus. BAC pretreatment prevented the increased α4β2 nicotinic receptor binding sites in the AcbSh, MHb, thalamic nuclei, DLG nucleus and fr. The present results suggest a relationship between BAC´s preventive effect of the expression of NIC withdrawal signs, and its ability to restore the changes in α4β2 nicotinic receptor labeling, evidenced in specific brain areas in NIC withdrawn animals.Fil: Varani, Andrés Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); ArgentinaFil: Antonelli, Marta Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencias "Profesor Eduardo de Robertis"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Balerio, Graciela Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; ArgentinaElsevier2013-07-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/2827Varani, Andrés Pablo; Antonelli, Marta Cristina; Balerio, Graciela Noemí; Mecamylamine-precipitated nicotine withdrawal syndrome and its prevention with baclofen: An autoradiographic study of α4β2 nicotinic acetylcholine receptors in mice; Elsevier; Progress of Neuro-psychopharmacology and Biological Psychiatry; 44; 01-7-2013; 217-2250278-5846enginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.pnpbp.2013.02.016info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0278584613000511info:eu-repo/semantics/altIdentifier/issn/0278-5846info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:44:11Zoai:ri.conicet.gov.ar:11336/2827instacron: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 09:44:12.118CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mecamylamine-precipitated nicotine withdrawal syndrome and its prevention with baclofen: An autoradiographic study of α4β2 nicotinic acetylcholine receptors in mice
title Mecamylamine-precipitated nicotine withdrawal syndrome and its prevention with baclofen: An autoradiographic study of α4β2 nicotinic acetylcholine receptors in mice
spellingShingle Mecamylamine-precipitated nicotine withdrawal syndrome and its prevention with baclofen: An autoradiographic study of α4β2 nicotinic acetylcholine receptors in mice
Varani, Andrés Pablo
[3h]Epibatidine
Baclofen
Nicotine
Α4β2 Nicotinic Receptor
Withdrawal
title_short Mecamylamine-precipitated nicotine withdrawal syndrome and its prevention with baclofen: An autoradiographic study of α4β2 nicotinic acetylcholine receptors in mice
title_full Mecamylamine-precipitated nicotine withdrawal syndrome and its prevention with baclofen: An autoradiographic study of α4β2 nicotinic acetylcholine receptors in mice
title_fullStr Mecamylamine-precipitated nicotine withdrawal syndrome and its prevention with baclofen: An autoradiographic study of α4β2 nicotinic acetylcholine receptors in mice
title_full_unstemmed Mecamylamine-precipitated nicotine withdrawal syndrome and its prevention with baclofen: An autoradiographic study of α4β2 nicotinic acetylcholine receptors in mice
title_sort Mecamylamine-precipitated nicotine withdrawal syndrome and its prevention with baclofen: An autoradiographic study of α4β2 nicotinic acetylcholine receptors in mice
dc.creator.none.fl_str_mv Varani, Andrés Pablo
Antonelli, Marta Cristina
Balerio, Graciela Noemí
author Varani, Andrés Pablo
author_facet Varani, Andrés Pablo
Antonelli, Marta Cristina
Balerio, Graciela Noemí
author_role author
author2 Antonelli, Marta Cristina
Balerio, Graciela Noemí
author2_role author
author
dc.subject.none.fl_str_mv [3h]Epibatidine
Baclofen
Nicotine
Α4β2 Nicotinic Receptor
Withdrawal
topic [3h]Epibatidine
Baclofen
Nicotine
Α4β2 Nicotinic Receptor
Withdrawal
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv A previous study from our laboratory showed that baclofen (BAC, GABAB receptor agonist) was able to prevent the behavioral expression of nicotine (NIC) withdrawal syndrome. To further investigate the mechanisms underlying this effect, we conducted this study, with the aims of analyzing α4β2 nicotinic receptor density during NIC withdrawal and, in case we found any changes, of determining whether they could be prevented by pretreatment with BAC. Swiss Webster albino mice received NIC (2.5 mg/kg, s.c.) 4 times daily, for 7 days. On the 8th day, NIC-treated mice received the nicotinic antagonist mecamylamine (MEC; 2 mg/kg, i.p.) 1 h after the last dose of NIC. A second group of NIC-treated mice received BAC (2 mg/kg, i.p.) prior to MEC administration. Thirty minutes after MEC, mice were sacrificed and brain autoradiography with [3H]epibatidine was carried out at five different anatomical levels. Autoradiographic mapping showed a significant increase of α4β2 nicotinic receptor labeling during NIC withdrawal in the nucleus accumbens shell (AcbSh), medial habenular nucleus (HbM), thalamic nuclei, dorsal lateral geniculate (DLG) nucleus, fasciculus retroflexus (fr), ventral tegmental area, interpeduncular nucleus and superior colliculus. BAC pretreatment prevented the increased α4β2 nicotinic receptor binding sites in the AcbSh, MHb, thalamic nuclei, DLG nucleus and fr. The present results suggest a relationship between BAC´s preventive effect of the expression of NIC withdrawal signs, and its ability to restore the changes in α4β2 nicotinic receptor labeling, evidenced in specific brain areas in NIC withdrawn animals.
Fil: Varani, Andrés Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); Argentina
Fil: Antonelli, Marta Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencias "Profesor Eduardo de Robertis"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Balerio, Graciela Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina
description A previous study from our laboratory showed that baclofen (BAC, GABAB receptor agonist) was able to prevent the behavioral expression of nicotine (NIC) withdrawal syndrome. To further investigate the mechanisms underlying this effect, we conducted this study, with the aims of analyzing α4β2 nicotinic receptor density during NIC withdrawal and, in case we found any changes, of determining whether they could be prevented by pretreatment with BAC. Swiss Webster albino mice received NIC (2.5 mg/kg, s.c.) 4 times daily, for 7 days. On the 8th day, NIC-treated mice received the nicotinic antagonist mecamylamine (MEC; 2 mg/kg, i.p.) 1 h after the last dose of NIC. A second group of NIC-treated mice received BAC (2 mg/kg, i.p.) prior to MEC administration. Thirty minutes after MEC, mice were sacrificed and brain autoradiography with [3H]epibatidine was carried out at five different anatomical levels. Autoradiographic mapping showed a significant increase of α4β2 nicotinic receptor labeling during NIC withdrawal in the nucleus accumbens shell (AcbSh), medial habenular nucleus (HbM), thalamic nuclei, dorsal lateral geniculate (DLG) nucleus, fasciculus retroflexus (fr), ventral tegmental area, interpeduncular nucleus and superior colliculus. BAC pretreatment prevented the increased α4β2 nicotinic receptor binding sites in the AcbSh, MHb, thalamic nuclei, DLG nucleus and fr. The present results suggest a relationship between BAC´s preventive effect of the expression of NIC withdrawal signs, and its ability to restore the changes in α4β2 nicotinic receptor labeling, evidenced in specific brain areas in NIC withdrawn animals.
publishDate 2013
dc.date.none.fl_str_mv 2013-07-01
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/11336/2827
Varani, Andrés Pablo; Antonelli, Marta Cristina; Balerio, Graciela Noemí; Mecamylamine-precipitated nicotine withdrawal syndrome and its prevention with baclofen: An autoradiographic study of α4β2 nicotinic acetylcholine receptors in mice; Elsevier; Progress of Neuro-psychopharmacology and Biological Psychiatry; 44; 01-7-2013; 217-225
0278-5846
url http://hdl.handle.net/11336/2827
identifier_str_mv Varani, Andrés Pablo; Antonelli, Marta Cristina; Balerio, Graciela Noemí; Mecamylamine-precipitated nicotine withdrawal syndrome and its prevention with baclofen: An autoradiographic study of α4β2 nicotinic acetylcholine receptors in mice; Elsevier; Progress of Neuro-psychopharmacology and Biological Psychiatry; 44; 01-7-2013; 217-225
0278-5846
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.pnpbp.2013.02.016
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0278584613000511
info:eu-repo/semantics/altIdentifier/issn/0278-5846
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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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