Baclofen prevented the changes in c-Fos and brain-derived neutrophic factor expressions during mecamylamine-precipitated nicotine withdrawal in mice

ANDRÉS P. VARANI; MOUTINHO MACHADO LIRANE; GRACIELA N. BALERIO

SYNAPSE

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2014 vol. 68 p. 508 - 517

0887-4476

Previous studies from our laboratory showed that baclofen (BAC, GABAB receptor agonist) prevented the behavioural and neurochemical alterations of nicotine (NIC) withdrawal syndrome. To further investigate the mechanisms underlying these effects, we analysed the c-Fos and brain-derived neutrophic factor (BDNF) expression during NIC withdrawal and its prevention with BAC. Swiss-Webster mice received NIC (2.5 mg/kg, sc) 4 times daily, for 7 days. On the 8th day, NIC-treated mice received the nicotinic antagonist mecamylamine (MEC; 2 mg/kg, ip) 1 hour after the last dose of NIC. A second group of NIC-treated mice received BAC (2 mg/kg, ip) prior to MEC administration. Thirty minutes after MEC, mice were sacrificed and the immunohistochemistry assays (c-Fos and BDNF) were carried out at different anatomical levels. c-Fos expression decreased in the dentate gyrus of the hippocampus (DG) and the bed nucleus of the stria terminalis (BST), and increased in the habenular (Hb), accumbens shell (AcbSh) nuclei during NIC withdrawal. BAC re-established the modified c-Fos expression only in the DG, BST and AcbSh during NIC withdrawal. On the other hand, BDNF expression decreased in the CA1 and CA3 area of the hippocampus, the Hb and caudate putamen (CPu) during NIC withdrawal. Finally, BAC restored the decreased BDNF expression during NIC withdrawal in the CA1, CA3, Hb and CPu. The results suggest a relationship between BAC?s preventive effect of the expression of NIC withdrawal signs, and its ability to restore the changes in c-Fos and BDNF expression, observed in specific brain areas of NIC-withdrawn mice.