NEUROENDOCRINE FACTORS AND BRAIN MECHANISMS IN OLFACTORY FUNCTION

尽管据报道许多药物会改变化学感觉功能

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.