ROLE OF THE GABAB RECEPTORS IN THE EFFECTS INDUCED BY NICOTINE ON ANXIETY-LIKE BEHAVIOUR IN MICE

VARANI A; CALVO M; MOUTINHO L; INDUNI A; BALERIO G

Rosario- Argentina

Congreso; XLI Reunión Anual de la Sociedad Argentina de Farmacología Experimental; 2009

SAFE

ROLE OF THE GABAB RECEPTORS IN THE EFFECTS INDUCED BY NICOTINE ON ANXIETY-LIKE BEHAVIOUR IN MICE Varani A 1, Calvo M 1, Moutinho L1, Induni A1,2 and Balerio G1,2 1ININFA (CONICET) y 2Cát. de Farmacología (FFYB, UBA) Junín 956, 5°Piso.  Buenos Aires. E-mail: gbalerio@ffyb.uba.ar   The aim of the present study was to evaluate the possible involvement of the GABAergic system in the anxiolytic- and anxiogenic-like responses induced by nicotine (NIC) in mice, using both pharmacological and genetic approaches. Animals were only exposed once to NIC. The acute administration of low (0.05 mg/kg, sc) or high (0.8 mg/kg, sc) doses of NIC produced opposite effects in the elevated plus maze, anxiolytic- anxiogenic-like responses, respectively. The effects of the pretreatment with the GABAB receptor antagonist, 2-OH Saclofen (SAC) (0.25, 0.5 and 1 mg/kg; ip) and the GABAB receptor agonist, baclofen (BAC) (0.5, 1 and 2 mg/kg; ip), were evaluated on the anxiolytic- and anxiogenic-like responses induced by NIC. SAC completely abolished these NIC-induced effects (p<0.001; p<0.01, respectively) at the higher dose, suggesting an involvement of GABAB receptor in these behavioural responses. On the other hand, BAC failed to modify the effects induced by NIC on anxiety-like behavior. In addition, in GABAB(1) knockout mice the anxiolytic-like responses of NIC were blocked (p<0.001), suggesting a role of GABAB(1) receptor in these behavioural responses, but not in the anxiogenic-like effects of NIC. These results demonstrate that the endogenous GABAergic system is involved in the regulation of NIC anxiety-like behaviour in mice and provide new findings to support a potential pharmaco therapeutic use of GABAergic drugs in the treatment of tobacco addiction. Supported by UBACYT B016