title: Lack of GABAB receptors modifies behavioural and biochemical alterations induced by precipitated nicotine withdrawal.
abstract: The nicotine (NIC) withdrawal syndrome is considered to be a major cause of the high relapse rate among individuals undergoing smoking cessation. The aim of the present study was to evaluate a possible role of GABAB receptors in NIC withdrawal, by comparing GABAB1 knockout mice and their wild-type littermates. We analysed the time course of the global withdrawal score, the anxiety-like effects, monoamine concentrations, the brain-derived neurotrophic factor (BDNF) expression, the corticosterone plasmatic levels and [(3)H]epibatidine binding sites during NIC withdrawal precipitated by mecamylamine, a nicotinic receptor antagonist (MEC). In NIC withdrawn wild-type mice, we observed a global withdrawal score, an anxiety-like effect in the elevated plus maze, a decrease of the striatal dopamine and 3,4-dihydroxyphenylacetic acid concentrations, an increase of corticosterone plasma levels, a reduction of BDNF expression in several brain areas and an increase of [(3)H]epibatidine binding sites in specific brain regions. Interestingly, the effects found in NIC withdrawn wild-type mice were absent in GABAB1 knockout mice, suggesting that GABAB1 subunit of the GABAB receptor is involved in the regulation of the behavioural and biochemical alterations induced by NIC withdrawal in mice. These results reveal an interaction between the GABAB receptors and the neurochemical systems through which NIC exerts its long-term effects.
authors.affiliation: Instituto de Investigaciones Farmacológicas (CONICET), Junín 956, 5° Piso, Buenos Aires C1113AAD, Argentina.
authors.forename: Andrés P
authors.initials: AP
authors.lastname: Varani
authors.affiliation: Instituto de Investigaciones Farmacológicas (CONICET), Junín 956, 5° Piso, Buenos Aires C1113AAD, Argentina.
authors.forename: Valeria T
authors.initials: VT
authors.lastname: Pedrón
authors.affiliation: Instituto de Investigaciones Farmacológicas (CONICET), Junín 956, 5° Piso, Buenos Aires C1113AAD, Argentina.
authors.forename: Lirane Moutinho
authors.initials: LM
authors.lastname: Machado
authors.affiliation: Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Marta C
authors.initials: MC
authors.lastname: Antonelli
authors.affiliation: Department of Biomedicine, Institute of Physiology, Pharmazentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bettler
authors.affiliation: Instituto de Investigaciones Farmacológicas (CONICET), Junín 956, 5° Piso, Buenos Aires C1113AAD, Argentina; Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 5° Piso, Buenos Aires C1113AAD, Argentina. Electronic address: gbalerio@ffyb.uba.ar.
authors.forename: Graciela N
authors.initials: GN
authors.lastname: Balerio
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000172:deficiency* / Q000235:genetics; D011978:Receptors, Nicotinic / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D014029:Tobacco Use Disorder / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C546266:Gabrb1 protein, mouse; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011963:Receptors, GABA-A; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D009538:Nicotine; D003345:Corticosterone
keywords: Anxiety; BDNF; Corticosterone; Epibatidine; GABA(B) receptor; Mice; Monoamines; Nicotine; Withdrawal