Behavioral and neurochemical variations during nicotine withdrawal in mice. Prevention with Baclofen

VARANI ANDRÉS P; MOUTINHO LIRANE; CALVO MARIELA; BALERIO GRACIELA

Huerta Grande, Córdoba

Congreso; I Reunión Conjunta de Neurociencias (IRCN); 2009

Behavioral and neurochemical variations during nicotine withdrawal in mice. Prevention with Baclofen. Varani, A.1; Moutinho L1; Calvo M1; Balerio G1-2 - 1ININFA (CONICET); 2Cát. de Farmacología (FFyB-UBA). Nicotine (NIC) is critical in the maintenance of tobacco use and is the major active component of tobacco. The aim of the present study was 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) 4 times daily, for 7 days. On day 8, dependent mice received the nicotine antagonist mecamylamine (MEC, 2 mg/kg, ip) 1 h 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 dopamine (DA), serotonin (5-HT) and its metabolites were determined by HPLC in the striatum, cortex and hippocampus. NIC withdrawal produced a significant increase in wet-dog-shakes (P<0.05) and paw tremors (P<0.01) at 10 min. BAC prevented the incidence of these withdrawal signs. The global withdrawal score was also attenuated by BAC (P<0.001). DA and DOPAC cortical levels decreased (P<0.05; P<0.001, respectively) in the abstinent group, while BAC reestablished these levels 10 min after NIC withdrawal. Furthermore, DA and 5-HT striatal levels decreased (P<0.01; P<0.01, respectively) during NIC withdrawal and BAC reestablished the decrease caused by the withdrawal. These results indicate that BAC prevents NIC withdrawal syndrome. This could be related to changes in dopaminergic and serotonergic activity measured 10 min after NIC withdrawal.