Ability of baclofen to prevent somatic manifestations and neurochemical changes during nicotine withdrawal

• Published in: Drug and alcohol dependence Vol. 119; no. 1; pp. e5 - e12
• Main Authors: Varani, Andrés P, Moutinho, Lirane Machado, Calvo, Mariela, Balerio, Graciela N
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.12.2011
• Subjects: Acetic acid; Animals; Baclofen; Baclofen - blood; Baclofen - pharmacology; Baclofen - therapeutic use; Bacterial artificial chromosomes; Behavior, Animal - drug effects; Cortex; Disease Models, Animal; Dopamine; Drug dependence; Drug Evaluation, Preclinical; GABAergic system; gamma -Aminobutyric acid B receptors; High-performance liquid chromatography; Hippocampus; Male; mecamylamine; Mecamylamine - adverse effects; Mecamylamine - blood; Metabolites; Mice; Motor Activity - drug effects; Neostriatum; Neurochemicals; Nicotine; Nicotine - adverse effects; Nicotine - blood; Nicotinic Agonists - adverse effects; Nicotinic Agonists - blood; Nicotinic Antagonists - adverse effects; Nicotinic Antagonists - blood; Psychiatry; Serotonin; Smoking; Smoking Cessation - methods; Substance Withdrawal Syndrome - drug therapy; Substance Withdrawal Syndrome - metabolism; Substance Withdrawal Syndrome - prevention & control; Time Factors; Tobacco; Withdrawal; Mice; GABAergic system; Withdrawal; Baclofen; Nicotine
• ISSN: 0376-8716; 1879-0046
• DOI: 10.1016/j.drugalcdep.2011.05.017

Abstract Background Nicotine (NIC), the major active component of tobacco, is critical in the maintenance of the smoking habit. The aims of the present study were to analyze the behavioural and neurochemical variations during NIC withdrawal syndrome in mice, and whether they are prevented with baclofen (BAC, GABAB receptor agonist). Methods Swiss-Webster albino mice received NIC (2.5 mg/kg, s.c.) 4 times daily, for 7 consecutive days. On day 8 (the day of the experiment), NIC-treated mice received the nicotine antagonist mecamylamine (MEC, 2 mg/kg, i.p.) 1 h after the last dose of NIC. A second group of dependent mice received BAC (2 mg/kg, i.p.) before MEC-precipitated abstinence. The somatic signs were measured for 30 min. Dopamine (DA), serotonin (5-hydroxytryptamine; 5-HT) and its metabolites concentrations were determined by HPLC in the striatum, cortex and hippocampus. Results The global score was greater in the abstinent group compared to the control group. Moreover, the global score time course showed a higher increase at 10 min compared to the global score at 5 min or 30 min after MEC-precipitated NIC withdrawal. In addition, the global score was attenuated by BAC. The DA and dihydroxyphenyl acetic acid (DOPAC) cortical levels decreased in the abstinent group, while BAC reestablished these levels 10 min after NIC withdrawal. Furthermore, DA and 5-HT striatal levels decreased during NIC withdrawal, and BAC reverted this decrease. Conclusion In conclusion, the prevention of NIC withdrawal signs by BAC could be related to changes in dopaminergic and serotonergic activity.