Project: Research project

Project Details


The overall aim of the proposed research is the elucidation of the
molecular mechanisms underlying the regulation of the brain opiod
systems. Mu, delta and K opioid receptors mediate the actions of
opioid drugs and the three classes of opioid peptides, beta-
endorphin, the enkephalins and dynorphin-related peptides, upon
nervous tissue. Experiments are designed to examine 1) the
regulation of opioid receptors and peptides in adult brain by
exogenously adminisstered opioids and 2) the regulation of the
expression of opioid receptors and peptides in development. this
laboratory has demonstrated that chronic antagonist treatment
produces a coordinated upregulation of mu and delta receptors and
an increase in enkephalin levels in several brain regions. Long-
term exposrue of cells to delta opioids is known to produce
receptor downregulation in vitro, but not in vivo. This research
proposal aims to extend these phenomenological observations to a
molecular mechanistic level. A combination of receptor
readioautographyc and molecular biological techniques will be
used to elucidate the molecular event s underlying opioid receptor
and peptide regulation in vivo. Specifically, the following
questions will be addressed: 1) Do exogenous opioids alter opioid
receptor and peptide synthesis rates? 2) Does this occur at the
transcriptional or translational levels? 3) Are opioid peptides and
receptors regulated differnetially throughout the brain? the
second section of the proposal aims to identify factors which
influence opioid receptor and peptide expression in development.
Primary cultures of striatal and hypothalamic neurons will be used
as model systems to study the effects of neuronotrophic factors,
innervation, cell-cell contact and target organ interactions upon
opioid receptor and peptide expression. Together, these studies
are expected to provide important new information about the
regulation of this major transmitter-receptor system of the
central nervous system and to elucidate mechanisms underlying
opioid tolerance and dependence.
Effective start/end date4/1/8712/31/90


  • Medicine(all)


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