CONICET | Buscador de Institutos y Recursos Humanos

BACLOFEN REESTABLISHES C-FOS EXPRESSION DURING NICOTINE WITHDRAWAL SYNDROME IN MICE Moutinho L 1, Induni A1,2, Varani A 1 and Balerio G1,2 1ININFA (CONICET) y 2Cát. de Farmacología, FFYB (UBA) Junín 956, 5°Piso. Buenos Aires. E-mail: gbalerio@ffyb.uba.ar C-Fos, a member of Fos family of transcription factors, is implicated in behavioural responses and synaptic plasticity induced by abused drugs. Our previous studies demonstrated that baclofen (BAC), GABAB receptor agonist, was able to prevent the somatic expression and reestablish the dopaminergic and serotonergic activity during NIC withdrawal syndrome in mice. The aim of the present study was to evaluate the immediate early gene c-Fos expression in various brain areas in mice during NIC withdrawal syndrome and its prevention with BAC. Swiss mice received NIC (2.5 mg/kg, sc) 4 times daily, for 7 days. On day 8th, dependent mice received the NIC receptor 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. Animals were anesthetized and transcardially perfused with paraformaldehyde. Brains were removed and cut to perform immunohistochemical studies. Our results showed a significant decrease in c-Fos expression in the dentate gyrus of hippocampus (p<0.05) and the bed nucleus of the stria terminalis (p<0.001) of NIC withdrawn mice vs control group. Conversely, the number of Fos-positive nuclei was significantly increased in the cingulate cortex. BAC was able to reestablish the expression of c-Fos in these brain areas of NIC withdrawal animals. In conclusion, the effect of BAC in preventing the somatic signs of NIC withdrawal could be related with changes in c-Fos expression. Supported by UBACYT B016