Baclofen prevented the changes in c-Fos and brain-derived neutrophic factor expressions during mecamylamine-precipitated nicotine withdrawal in mice

Previous studies from our laboratory showed that baclofen (BAC, GABAB receptor agonist) prevented the behavioral and neurochemical alterations of nicotine (NIC) withdrawal syndrome. To further investigate the mechanisms underlying these effects, we analyzed the c-Fos and brain-derived neutrophic fac...

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Authors: Varani, Andrés P.; Machado Moutinho, Lirane; Balerio, Graciela Noemí
Format: Article
Status:Published version
Publication date:2014
Country:Argentina
Institution:Consejo Nacional de Investigaciones Científicas y Técnicas
Repository:CONICET Digital (CONICET)
Language:English
OAI Identifier:oai:ri.conicet.gov.ar:11336/13636
Online Access:http://hdl.handle.net/11336/13636
Access Level:Open access
Keyword:Abstinence
Gabab Receptors
Gabaergic System
Immediate Early Gene Expression
Neurotrophic Factors
https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
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author Varani, Andrés P.
author2 Machado Moutinho, Lirane
Balerio, Graciela Noemí
author2_role author
author
author_browse Balerio, Graciela Noemí
Machado Moutinho, Lirane
Varani, Andrés P.
author_facet Varani, Andrés P.
Machado Moutinho, Lirane
Balerio, Graciela Noemí
author_role author
collection CONICET Digital (CONICET)
description Previous studies from our laboratory showed that baclofen (BAC, GABAB receptor agonist) prevented the behavioral and neurochemical alterations of nicotine (NIC) withdrawal syndrome. To further investigate the mechanisms underlying these effects, we analyzed the c-Fos and brain-derived neutrophic factor (BDNF) expression during NIC withdrawal and its prevention with BAC. Swiss-Webster mice received NIC (2.5 mg/kg, sc) four 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 the immunohistochemistry assays (c-Fos and BDNF) were performed at different anatomical levels. c-Fos expression decreased in the dentate gyrus of the hippocampus (DG) and the bed nucleus of the stria terminalis (BST), and increased in the habenular (Hb), accumbens shell (AcbSh) nuclei during NIC withdrawal. BAC re-established the modified c-Fos expression only in the DG, BST and AcbSh during NIC withdrawal. Conversely, BDNF expression decreased in the CA1 and CA3 area of the hippocampus, the Hb, and caudate putamen (CPu) during NIC withdrawal. Finally, BAC restored the decreased BDNF expression during NIC withdrawal in the CA1, CA3, Hb, and CPu. The results suggest a relationship between BAC's preventive effect of the expression of NIC withdrawal signs, and its ability to restore the changes in c-Fos and BDNF expression, observed in specific brain areas of NIC-withdrawn mice.
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identifier_str_mv Varani, Andrés P.; Machado Moutinho, Lirane; Balerio, Graciela Noemí; Baclofen prevented the changes in c-Fos and brain-derived neutrophic factor expressions during mecamylamine-precipitated nicotine withdrawal in mice; Wiley; Synapse; 68; 11; 6-2014; 508-517
0887-4476
institution Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
language eng
network_acronym_str AR
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oai_identifier_str oai:ri.conicet.gov.ar:11336/13636
publishDate 2014
publishDateSort 2014
publisher Wiley
publisherStr Wiley
reponame_str CONICET Digital (CONICET)
spelling Baclofen prevented the changes in c-Fos and brain-derived neutrophic factor expressions during mecamylamine-precipitated nicotine withdrawal in mice Varani, Andrés P. Machado Moutinho, Lirane Balerio, Graciela Noemí Abstinence Gabab Receptors Gabaergic System Immediate Early Gene Expression Neurotrophic Factors https://purl.org/becyt/ford/3.3 https://purl.org/becyt/ford/3 Previous studies from our laboratory showed that baclofen (BAC, GABAB receptor agonist) prevented the behavioral and neurochemical alterations of nicotine (NIC) withdrawal syndrome. To further investigate the mechanisms underlying these effects, we analyzed the c-Fos and brain-derived neutrophic factor (BDNF) expression during NIC withdrawal and its prevention with BAC. Swiss-Webster mice received NIC (2.5 mg/kg, sc) four 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 the immunohistochemistry assays (c-Fos and BDNF) were performed at different anatomical levels. c-Fos expression decreased in the dentate gyrus of the hippocampus (DG) and the bed nucleus of the stria terminalis (BST), and increased in the habenular (Hb), accumbens shell (AcbSh) nuclei during NIC withdrawal. BAC re-established the modified c-Fos expression only in the DG, BST and AcbSh during NIC withdrawal. Conversely, BDNF expression decreased in the CA1 and CA3 area of the hippocampus, the Hb, and caudate putamen (CPu) during NIC withdrawal. Finally, BAC restored the decreased BDNF expression during NIC withdrawal in the CA1, CA3, Hb, and CPu. The results suggest a relationship between BAC's preventive effect of the expression of NIC withdrawal signs, and its ability to restore the changes in c-Fos and BDNF expression, observed in specific brain areas of NIC-withdrawn mice. Fil: Varani, Andrés P.. 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 Fil: Machado Moutinho, Lirane. 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 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 Wiley http://hdl.handle.net/11336/13636 Varani, Andrés P.; Machado Moutinho, Lirane; Balerio, Graciela Noemí; Baclofen prevented the changes in c-Fos and brain-derived neutrophic factor expressions during mecamylamine-precipitated nicotine withdrawal in mice; Wiley; Synapse; 68; 11; 6-2014; 508-517 0887-4476
spellingShingle Baclofen prevented the changes in c-Fos and brain-derived neutrophic factor expressions during mecamylamine-precipitated nicotine withdrawal in mice
Varani, Andrés P.
Abstinence
Gabab Receptors
Gabaergic System
Immediate Early Gene Expression
Neurotrophic Factors
https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
status_str publishedVersion
title Baclofen prevented the changes in c-Fos and brain-derived neutrophic factor expressions during mecamylamine-precipitated nicotine withdrawal in mice
title_full Baclofen prevented the changes in c-Fos and brain-derived neutrophic factor expressions during mecamylamine-precipitated nicotine withdrawal in mice
title_fullStr Baclofen prevented the changes in c-Fos and brain-derived neutrophic factor expressions during mecamylamine-precipitated nicotine withdrawal in mice
title_full_unstemmed Baclofen prevented the changes in c-Fos and brain-derived neutrophic factor expressions during mecamylamine-precipitated nicotine withdrawal in mice
title_short Baclofen prevented the changes in c-Fos and brain-derived neutrophic factor expressions during mecamylamine-precipitated nicotine withdrawal in mice
title_sort Baclofen prevented the changes in c-Fos and brain-derived neutrophic factor expressions during mecamylamine-precipitated nicotine withdrawal in mice
topic Abstinence
Gabab Receptors
Gabaergic System
Immediate Early Gene Expression
Neurotrophic Factors
https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
topic_facet Abstinence
Gabab Receptors
Gabaergic System
Immediate Early Gene Expression
Neurotrophic Factors
https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
url http://hdl.handle.net/11336/13636