OPIOID RECEPTORS IN COCHLEAR NUCLEUS

Texas Woman'S University, Denton TX

Investigators

Abstract

DESCRIPTION: (Adapted from the Investigator's Abstract) In the central nervous system, opioid peptides and their receptors appear to modulate a wide variety of physiological processes including attention, drive, mood , reproduction and responses to stress. They have also been found in primary sensory nuclei where they are involved in the filtering and processing of sensory information. Additionally, they have been implicated in the regulation of neuronal development. One means by which opioid peptides (e.g., dynorphin and the enkephalins) or activation of their receptors (kappa- and delta- opioid receptors, respectively) exert their cellular effects is through the regulation of intracellular calcium concentration ([Ca2+]i). An increase in [Ca2+]i can lead to nerve cell death in many parts of the nervous system. For example, in the chick cochlear nucleus, Nucleus Magnocellularis (NM), cessation of excitatory input by unilateral cochlea removal results in a large increase in [Ca2+]i within 1 hr and a subsequent loss of 30% of its neurons compared to the those on the unoperated side of the brain. Understanding the ways that nerve cells can prevent an increase in [Ca2+]i may lead to strategies to prevent neuronal death. In neurons of the chick NM, kappa-opioid receptor (KOR) activation results in a 25% decrease in [Ca2+]i from baseline values. Although pharmacological evidence suggests that KORs exist in NM, anatomical data is lacking. the long-term goals of the research are to investigate the roles of opioid receptor activation in the regulation of calcium homeostasis, neuronal development and sensory processing in the chick N, a relatively simple model system whose physiology and anatomy are well characterized and better understood than its mammalian homologue. As a first step toward those ends, the specific aims of this project are to use immunohistochemical and receptor binding techniques to examine the localization of opioid receptors in the chick NM, to describe their spatial distribution across this nucleus, and to study changes in their expression during development and after deafferentation. This research is significant not only for possibly preventing the nerve cell loss that results in some types of sensorineural deafness, but also in other neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's disease.