新的研究表明许多被诊断患有精神分裂症的患者——其中很大比例的患者不断吸香烟——由于尼古丁对认知功能的治疗属性而滥用烟草。尽管已知尼古丁可以通过增加一种称为谷氨酸脱羧酶67（GAD67）的蛋白质功能从而影响大脑的化学性质——精神分裂症患者大脑中的这种蛋白质异常偏低——它的准确的机制尚不清楚。
Rosalba Satta及其同事发现，不断给小鼠皮下注射尼古丁会通过合成抑制性神经递质γ-氨基丁酸（GABA）从而增加额叶的GAD67的表达。与正常人相比，精神分裂症患者的GABA含量减少。这组作者证明了尼古丁通过提高额叶的上面两层的GAD67从而增加了GABA的制造。用一种能轻易穿过血脑屏障的药物美加明预先治疗小鼠，这会阻断尼古丁引起的GAD67表达增加。
这组科学家提出，通过作用于氨基丁酸能神经元上的烟碱型乙酰胆碱受体，尼古丁增加了GAD67的表达，这可能有助于减轻精神分裂症典型的幻觉，精神分裂症被认为和氨基丁酸能神经传递的缺乏有关。（生物谷Bioon.com）
生物谷推荐原始出处：
PNAS published October 13, 2008, doi:10.1073/pnas.0808699105
Nicotine decreases DNA methyltransferase 1 expression and glutamic acid decarboxylase 67 promoter methylation in GABAergic interneurons
R. Satta, E. Maloku, A. Zhubi, F. Pibiri, M. Hajos, E. Costa, and A. Guidotti
Tobacco smoking is frequently abused by schizophrenia patients (SZP). The major synaptically active component inhaled from cigarettes is nicotine, hence the smoking habit of SZP may represent an attempt to use nicotine self-medication to correct (i) a central nervous system nicotinic acetylcholine receptor (nAChR) dysfunction, (ii) DNA-methyltransferase 1 (DMT1) overexpression in GABAergic neurons, and (iii) the down-regulation of reelin and GAD67 expression caused by the increase of DNMT1-mediated hypermethylation of promoters in GABAergic interneurons of the telencephalon. Nicotine (4.5–22 μmol/kg s.c., 4 injections during the 12-h light cycle for 4 days) decreases DNMT1 mRNA and protein and increases GAD67 expression in the mouse frontal cortex (FC). This nicotine-induced decrease of DNMT1 mRNA expression is greater (80%) in laser microdissected FC layer I GABAergic neurons than in the whole FC (40%), suggesting selectivity differences for the specific nicotinic receptor populations expressed in GABAergic neurons of different cortical layers. The down-regulation of DNMT1 expression induced by nicotine in the FC is also observed in the hippocampus but not in striatal GABAergic neurons. Furthermore, these data show that in the FC, the same doses of nicotine that decrease DNMT1 expression also (i) diminished the level of cytosine-5-methylation in the GAD67 promoter and (ii) prevented the methionine-induced hypermethylation of the same promoter. Pretreatment with mecamylamine (6 μmol/kg s.c.), an nAChR blocker that penetrates the blood–brain barrier, prevents the nicotine-induced decrease of FC DNMT1 expression. Taken together, these results suggest that nicotine, by activating nAChRs located on cortical or hippocampal GABAergic interneurons, can up-regulate GAD67 expression via an epigenetic mechanism. Nicotine is not effective in striatal medium spiny GABAergic neurons that primarily express muscarinic receptors.
