期刊
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
卷 44, 期 -, 页码 217-225出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2013.02.016
关键词
[H-3]epibatidine; Baclofen; Nicotine; Withdrawal; alpha(4)beta(2) nicotinic receptor
资金
- UBACyT from University of Buenos Aires [B016]
- CONICET [PIP 11420090100303]
- University of Buenos Aires [677/10]
- ANPCYT [PICT 0040]
A previous study from our laboratory showed that baclofen (BAC, GABA(B) receptor agonist) was able to prevent the behavioral expression of nicotine (NIC) withdrawal syndrome. To further investigate the mechanisms underlying this effect, we conducted this study, with the aims of analyzing alpha(4)beta(2) nicotinic receptor density during NIC withdrawal and, in case we found any changes, of determining whether they could be prevented by pretreatment with BAC. Swiss Webster albino mice received NIC (2.5 mg/kg, s.c.) 4 times daily, for 7 days. On the 8th day, NIC-treated mice received the nicotinic antagonist mecamylamine (MEC; 2 mg/kg, i.p.) 1 h after the last dose of NIC A second group of NIC-treated mice received BAC (2 mg/kg, i.p.) prior to MEC administration. Thirty minutes after MEC, mice were sacrificed and brain autoradiography with [H-3]epibatidine was carried out at five different anatomical levels. Autoradiographic mapping showed a significant increase of alpha(4)beta(2) nicotinic receptor labeling during NIC withdrawal in the nucleus accumbens shell (AcbSh), medial habenular nucleus (HbM), thalamic nuclei, dorsal lateral geniculate (DLG) nucleus, fasciculus retroflexus (fr), ventral tegmental area, interpeduncular nucleus and superior colliculus. BAC pretreatment prevented the increased alpha(4)beta(2) nicotinic receptor binding sites in the AcbSh, MHb, thalamic nuclei, DLG nucleus and fr. The present results suggest a relationship between BAC's preventive effect of the expression of NIC withdrawal signs, and its ability to restore the changes in alpha(4)beta(2) nicotinic receptor labeling, evidenced in specific brain areas in NIC withdrawn animals. (C) 2013 Elsevier Inc. All rights reserved.
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