School of Biological Sciences, Centre for Biodiscovery, Department of Science, Victoria University of Wellington, Wellington, 6140, New Zealand.
Synapse. 2014 Feb;68(2):45-60. doi: 10.1002/syn.21715. Epub 2013 Sep 30.
Cigarette smoking is the leading cause of preventable death worldwide. Recently, tobacco extracts have been shown to have a different pharmacological profile to nicotine alone and there is increasing evidence of a role for non-nicotinic components of cigarette smoke in smoking addiction. Nicotine is known to affect the uptake of dopamine in the brain of laboratory animals, but studies in the literature are often contradictory and little is known of the effects on non-nicotinic tobacco components on dopamine uptake. This study has examined the acute and chronic effects of nicotine and a tobacco extract (TPM) on dopamine uptake by the dopamine and norepinephrine transporters (DAT and NET) ex vivo using rotating disk electrode voltammetry, and quantified DAT and NET protein and mRNA expression in key brain regions. Nicotine (0.35 mg/kg) significantly decreased DAT function in the nucleus accumbens (NAc) at 30 min with no change in protein expression. This effect was sensitive to mecamylamine and DHβE but not MLA, indicating that it is dependent on α4 subunit containing nicotinic receptors. Furthermore, TPM, but not nicotine, increased DAT function in the dorsal striatum at 1 h in a nicotinic receptor independent manner with no change in DAT protein expression. At 1 h DAT mRNA in the ventral tegmental area was decreased by both acute and chronic TPM treatments.
吸烟是全球可预防死亡的主要原因。最近，烟草提取物的药理学特性与尼古丁不同，越来越多的证据表明，香烟中的非尼古丁成分在吸烟成瘾中起作用。已知尼古丁会影响实验室动物大脑中多巴胺的摄取，但文献中的研究往往相互矛盾，对非尼古丁烟草成分对多巴胺摄取的影响知之甚少。本研究使用旋转圆盘电极伏安法，体外研究了尼古丁和烟草提取物（TPM）对多巴胺和去甲肾上腺素转运体（DAT 和 NET）摄取多巴胺的急性和慢性影响，并定量分析了关键脑区中 DAT 和 NET 蛋白和 mRNA 的表达。尼古丁（0.35mg/kg）在 30 分钟时显著降低了伏隔核（NAc）中的 DAT 功能，而蛋白表达没有变化。这种作用对美加明和 DHβE 敏感，但对 MLA 不敏感，表明它依赖于含有α4 亚基的烟碱型受体。此外，TPM（而非尼古丁）以不依赖烟碱型受体的方式在 1 小时增加了背侧纹状体中的 DAT 功能，DAT 蛋白表达没有变化。在 1 小时时，急性和慢性 TPM 处理均降低了腹侧被盖区的 DAT mRNA。
