CONICET | Buscador de Institutos y Recursos Humanos

INVOLVEMENT OF GABAERGIC SYSTEM IN NICOTINE WITHDRAWAL: SOMATIC AND NEUROCHEMICAL VARIATIONS Varani A 1, Moutinho L 1, Calvo M 1 and Balerio G1,2 1ININFA (CONICET) y 2Cát. de Farmacología (FFYB, UBA) Junín 956, 5°Piso. Bs As E-mail: gbalerio@ffyb.uba.ar Nicotine (NIC) plays a major role in tobacco addiction. The aims of the present study were: a) to evaluate the possible involvement of GABAergic system 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 mice received NIC (2.5 mg/kg, sc) 4 times daily, for 7 days. On day 8, dependent mice received the NIC antagonist mecamylamine (MEC; 2 mg/kg, ip) 1h after the last dose of NIC. 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 DA, 5-HT and its metabolites were determined by HPLC in the striatum, cortex and hippocampus of brains collected 10 min after the last injection on day 8, since NIC withdrawal response reached a maximum between 10 and 15 min. 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). DA and DOPAC levels decreased in the cortex of the abstinent group (p<0.001 and p<0.01 respectively), while BAC reestablished these levels 10 min after MEC-precipitated NIC withdrawal (p<0.01). We conclude that BAC prevents NIC withdrawal syndrome due to changes in dopaminergic activity measured 10 min after MEC. Supported by UBACYT B021 and B016. Presentación: POSTER