CONICET | Buscador de Institutos y Recursos Humanos

NICOTINE WITHDRAWAL SYNDROME AND PREVENTION WITH BACLOFEN: SOMATIC AND NEUROCHEMICAL ALTERATIONS Varani, A.1; Moutinho L1; Calvo M1; Balerio G2 - 1ININFA (CONICET) - Pharmacology; 2ININFA (CONICET) - Cát. de Farmacología, Fac. de Farmacia y Bioquímica, Universidad de Buenos Aires - Pharmacology Nicotine (NIC) is one of the active components of tobacco and plays a major role in tobacco addiction. The aims of the present study were: a) to evaluate the possible role of GABAB receptor in NIC physical dependence; b) to analyze the neurochemical variations in various brain regions of mice during NIC withdrawal syndrome and its prevention with baclofen (BAC, GABAB receptor agonist). Swiss-Webster albino mice received NIC (2.5 mg/kg, sc) four times daily, for seven consecutive days. To precipitate NIC abstinence, dependent mice were injected with the nicotine antagonist mecamylamine (MEC, 2 mg/kg, ip) 60 min after the last dose of NIC on the 8th day. A second group of dependent mice received BAC (2 mg/kg, ip) before MEC- precipitated abstinence. Somatic signs were measured for 30 min. The levels of dopamine, serotonin and its metabolites were determined by HPLC-coupled electrochemical detection in the striatum, cortex and hippocampus. BAC pre-treatment decreased the incidence of some NIC withdrawal signs, such as wet-dog-shakes (p<0.01) and paw tremors (p<0.001). The global withdrawal score was also attenuated by BAC (p<0.001). On the other hand, dopamine and DOPAC levels decreased in the abstinent group, while BAC reestablished these levels 10 min after MEC-precipitated nicotine withdrawal. These results indicate that BAC prevents NIC withdrawal syndrome. This would be related to changes in dopaminergic activity measured 10 min after MEC. Keywords: Nicotine - Abstinence - GABAergic system - Neurochemical changesSupported by: UBACYT B021 and Fundación Florencio Fiorini