CONICET | Buscador de Institutos y Recursos Humanos

BACLOFEN REESTABLISHED NICOTINE RECEPTOR (α4β2) LEVELS MODIFIED BY NICOTINE WITHDRAWAL IN MICE. Varani A. P.1-3, Antonelli M. C.2 and Balerio G. N.1-3 - 1ININFA (CONICET); 2IQUIFIB (CONICET); 3Cát. de Farmacología (Facultad de Farmacia y Bioquímica-UBA). Junin 956, 5º piso, (C1113AAD), Buenos Aires, Argentina. A previous study of our laboratory showed that baclofen (BAC, GABAB receptor agonist) was able to prevent the behavioural expression of nicotine (NIC) withdrawal syndrome. Taking into account this result, the aims of the present study were to analyze the density of nicotinic receptors (α4β2) in various brain regions of mice during NIC withdrawal and to evaluate whether the pretreatment with BAC is able to modify the nicotinic receptor (α4β2) levels altered during NIC withdrawal. Swiss-Webster albino mice received NIC (2.5 mg/kg, sc) 4 times daily, for 7 days. On the 8thday, dependent mice received the nicotinic antagonist mecamylamine (MEC; 2 mg/kg, ip) 1hour after the last dose of NIC. A second group of dependent mice received BAC (2 mg/kg, ip) previous to MEC administration. Thirty minutes after MEC, mice were sacrificed and autoradiography with [3H]epibatidine was carried out on mice brains at five different anatomical levels. Autoradiographic mapping showed a significant increase of nicotinic receptor (α4β2) labeling during NIC withdrawal in the medial habenular nucleus (HbM) (P<0.001) and in the interpeduncular nucleus (P<0.05). BAC pretreatment reestablished nicotinic receptor (α4β2) binding sites during NIC withdrawal only in the HbM (P<0.01). The present results suggest that the effect of BAC in preventing the expression of NIC withdrawal signs could be related with the ability of BAC to reestablish the nicotinic receptor (α4β2) labeling in certain brain areas. Supported by UBACYT B016 and PIP Nº 11420090100303 (CONICET).