NEUROENDOCRINE FACTORS AND BRAIN MECHANISMS IN OLFACTORY FUNCTION

尽管据报道，许多药物改变了患者的化学感觉功能 人类，令人惊讶的是，关于这一点的实证研究很少。 这在一定程度上是由于(I)很难从人类身上确定 临床调查研究，化学感觉改变是否由于 (Ii)该药物或其处方所针对的精神障碍； 在许多患者组中使用多种药物，以及(Iii) 在人类身上进行受控良好的双盲研究的成本很高， 尤其是当这种变化是微妙的和一系列药物剂量时 需要探索。出于这些原因，我们已经启动了研究 在这个项目中系统地评估- 对气味有明确生理作用的药物 大鼠的检测和辨别能力。特别感兴趣的 对我们来说，是影响多巴胺能系统的药物，给定 特发性帕金森病与嗅觉的关系 功能障碍，以及我们在上一次赠款期间的发现：(I) D-1激动剂SKF 38393增强大鼠的气味检测能力，(Ii) D-2激动剂螺环酮抑制这种表现，以及(Iii) 球内注射神经毒剂6-羟基多巴胺(6-OHDA)， 它消耗球部去甲肾上腺素，但不消耗多巴胺，没有 对气味检测性能的明显影响。在下一次 资助期我们将继续进行与多巴胺相关的研究 对嗅觉功能的影响。此外，我们将(I)延长我们的 研究有助于确定我们发现的特殊性，以及(Iii) 确定雌激素、皮质类固醇和抗氧化剂是否可以保护 大鼠嗅觉系统的功能和组织学损伤 3-甲基吲哚。我们的兴趣在于确定雌激素是否能保护 来自我们最近的发现，在一项对750人的研究中， 中心诊所的患者，(I)出乎意料的低数量 出现嗅觉障碍的绝经后妇女服用 结合雌激素(相对于一般妇女的百分比 服用这种雌激素的人口)和(Ii)向 有嗅觉系统投诉的中心，以及谁在服用共轭药物 与非雌激素摄入相比，雌激素表现出的功能障碍更少 对口单位。总体而言，对这一计划的研究将(I)导致 更好地了解药理药物对人的影响 嗅觉能力，(Ii)提供潜在的保护手段 嗅觉系统免受环境损害，以及(Iii)协助 在某些形式的嗅觉治疗策略的发展中 功能障碍。

Although numerous medications reportedly alter chemosensory function in humans, surprisingly few empirical studies are available on this point. This is due, in part, to (i) the difficulty in determining, from human clinical survey studies, whether the chemosensory alteration is due to the medication or to the disorder for which it is being prescribed, (ii) the use of multiple medications in many patients groups, and (iii) the high cost of performing well-controlled double-blind studies in humans, particularly when such alterations are subtle and a range of drug doses needs to be explored. For these reasons, we have initiated studies within this program to evaluate the influences of systemically- administered drugs with well-defined physiologic actions on the odor detection and discrimination performance of rats. Of particular interest to us are agents which influence the dopaminergic system, given the association between idiopathic Parkinson's disease and olfactory dysfunction, and our findings, during the last grant period, that (i) the D-1 agonist SKF 38393 enhances odor detection performance in rats, (ii) the D-2 agonist spiperone depresses such performance, and (iii) intrabulbar infusion of the neurotoxic agent 6-hydroxydopamine (6-OHDA), which depletes bulbar norepinephrine but not dopamine, has no demonstrable influence on odor detection performance. During the next funding period we will continue our studies of dopamine-related influences on olfactory function. In addition, we will (i) extend our studies of help determine the specificity of our findings, and (iii) establish whether estrogens, corticosteroids and antioxidants can protect the olfactory system from functional and histological damage induced by 3-methylindole. Our interest in determining whether estrogens protect against such damage stems from our recent findings, in a study of 750 Center clinic patients, that (i) an unexpectedly low number of postmenopausal women presenting with olfactory dysfunction were taking conjugated estrogens (relative to the percentage of women in the general population who take such estrogens) and (ii) women who presented to the Center with olfactory system complaints and who were taking conjugated estrogens evidenced less dysfunction than their non-estrogen taking counterparts. Overall, the studies of this program will (i) lead to a better understanding of the influences of pharmacologic agents on the ability to smell, (ii) provide potential means for protecting the olfactory system from environmentally-induced damage, and (iii) assist in the development of treatment strategies for some forms of olfactory dysfunction.