Lack of GABAB receptors modifies behavioural and biochemical alterations induced by precipitated nicotine withdrawal

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 GABA(B) receptors in NIC withdrawal, by comparing GABA(B1) 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 [H-3]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 In NIC withdrawn wild-type mice, we observed a global withdrawal score, an anxiety-like effect in the elevated plus maze, a decrease of the striatal dopamine and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 [H-3]epibatidine binding sites in specific brain regions. Interestingly, the effects found in NIC withdrawn wild-type mice were absent in GABA(B1) knockout mice, suggesting that GABA(B1) subunit of the GABA(B) receptor is involved in the regulation of the behavioural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 GABA(B) receptors and the neurochemical systems through which NIC exerts its long-term effects. (C) 2014 Elsevier Ltd. All rights reserved.