NEUROENDOCRINE FACTORS AND BRAIN MECHANISMS IN OLFACTORY FUNCTION

尽管许多药物据报道会改变化学感受功能， 人类，令人惊讶的是很少有实证研究可在这一点上。 这是由于，部分原因是（i）难以确定，从人类 临床调查研究，化学感觉改变是否是由于 （ii）该药物或该药物所针对的病症， 在许多患者群体中使用多种药物，以及（iii） 在人类中进行良好对照的双盲研究的成本很高， 特别是当这种变化是微妙的， 需要探索。 基于这些原因，我们已经开始研究 在这个项目中，系统地评估了 给予对气味具有明确生理作用的药物 大鼠的检测和辨别性能。 特别感兴趣的 对我们来说是影响多巴胺能系统的药物， 原发性帕金森病与嗅觉的关系 在最后一次拨款期间，我们的发现是（i） D-1激动剂SKF 38393增强大鼠的气味检测性能，（ii） D-2激动剂螺哌隆抑制这种性能，和（iii） 眼球内输注神经毒剂6-羟基多巴胺（6-OHDA）， 它消耗延髓去甲肾上腺素而不是多巴胺， 对气味检测性能的明显影响。 在下一个 在资助期间，我们将继续研究多巴胺相关的 影响嗅觉功能。 此外，我们将（i）扩大我们的 研究有助于确定我们发现的特异性，以及（iii） 确定雌激素、皮质类固醇和抗氧化剂是否可以保护 嗅觉系统功能和组织学损伤 3-甲基吲哚 我们对确定雌激素是否能保护 我们最近的一项研究发现， 中心诊所患者，（i）意外低数量 出现嗅觉功能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 （二）服用这种雌激素的妇女; 中心与嗅觉系统投诉和谁正在服用共轭 服用雌激素比不服用雌激素的人功能障碍少 同行 总的来说，这项计划的研究将（i）导致一个 更好地了解药物对 （二）提供潜在的保护手段， 嗅觉系统免受环境引起的损害，以及（iii）协助 在某些形式的嗅觉障碍的治疗策略的发展中， 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.