Tillerson Jennifer L, Caudle W Michael, Parent Jack M, Gong C, Schallert Timothy, Miller Gary W
Center for Neurodegenerative Disease, Emory University, Atlanta, GA 30322, USA.
Behav Brain Res. 2006 Sep 15;172(1):97-105. doi: 10.1016/j.bbr.2006.04.025. Epub 2006 Jun 9.
Previous pharmacological studies have implicated dopamine as a modulator of olfactory bulb processing. Several disorders characterized by altered dopamine homeostasis in olfaction-related brain regions display olfactory deficits. To further characterize the role of dopamine in olfactory processing, we subjected dopamine transporter knockout mice (DAT -/-) and dopamine receptor 2 knockout mice (D2 -/-) to a battery of olfactory tests. In addition to behavioral characterization, several neurochemical markers of olfactory bulb integrity and function were examined. DAT -/- mice displayed an olfactory discrimination deficit, but did not differ detectably from DAT wildtype (DAT +/+) mice in odor habituation, olfactory sensitivity, or odor recognition memory. Neurochemically, DAT -/- mice have decreased D2 receptor staining in the periglomerular layer of the olfactory bulb and increased tyrosine hydroxylase immunoreactivity compared to DAT +/+ controls. D2 -/- mice exhibited the same olfactory deficit as the DAT -/- mice, further supporting the role of dopamine at the D2 synapse in olfactory discrimination processing. The findings presented in this paper reinforce the functional significance of dopamine and more specifically the D2 receptor in olfactory discrimination and may help explain the behavioral phenotype in the DAT and D2 knockout mice.
以往的药理学研究表明多巴胺是嗅球处理过程的一种调节因子。几种以嗅觉相关脑区多巴胺稳态改变为特征的疾病表现出嗅觉缺陷。为了进一步明确多巴胺在嗅觉处理中的作用，我们对多巴胺转运体基因敲除小鼠（DAT -/-）和多巴胺受体2基因敲除小鼠（D2 -/-）进行了一系列嗅觉测试。除了行为特征分析外，还检测了嗅球完整性和功能的几种神经化学标志物。DAT -/-小鼠表现出嗅觉辨别缺陷，但在气味习惯化、嗅觉敏感性或气味识别记忆方面与DAT野生型（DAT +/+）小鼠没有明显差异。在神经化学方面，与DAT +/+对照组相比，DAT -/-小鼠嗅球小球周围层的D2受体染色减少，酪氨酸羟化酶免疫反应性增加。D2 -/-小鼠表现出与DAT -/-小鼠相同的嗅觉缺陷，进一步支持了多巴胺在D2突触处对嗅觉辨别处理的作用。本文的研究结果强化了多巴胺尤其是D2受体在嗅觉辨别中的功能意义，并可能有助于解释DAT和D2基因敲除小鼠的行为表型。
