Project: Research project

Project Details


DESCRIPTION: The long-term goal of the proposal is to understand the
cellular actions of estrogen and morphine on hypothalamic neurosecretory
neurons which control anterior pituitary secretions. The application
is based upon an ongoing NIDA- funded research program regarding the
electrophysiology of hypothalamic neurosecretory neurons. The Principal
Investigator is now seeking to increase the power of his techniques by
including whole-cell patch recordings. This will greatly expand the
candidate's research capabilities and is in keeping with his career
development plans. The proposal has a training and research component. The award would
allow the applicant to increase his time in the laboratory and to
receive training in vital new biological techniques. The research
component of the application seeks to further our understanding of the
role of estrogens in controlling neurosecretory neurons of the
hypothalamus. Since estrogen appears to decrease the number of
functional mu opioid receptors in a manner similar to chronic morphine
treatment, the research focuses on the interaction of and the common
cellular components affected by both agents. Hypothalamic slices will
be prepared from ovariectomized female guinea pigs which have been
treated with morphine or placebo. The first series of experiments will
study the interaction of chronic morphine in vivo and acute estrogen in
vitro in altering the mu opioid mediated membrane hyperpolarization of
identified arcuate (ARC) neurons by measuring the shift in the mu opioid
dose-response curve in the two groups of animals.Cells from morphine-
treated or placebo- treated, ovariectomized (oil-treated) guinea pigs
will be tested with mu opioid agonists before and after perfusion with
17 Beta-estradiol. The time- course and site of estrogen's rapid actions
to decrease the potency of the mu opioid response will also be
determined. Finally, the effects of chronic morphine on a heterologous
receptor response (GABA-B) which is coupled to the inwardly rectifying
K channel and affected by estrogen will be measured. Other experiments
will study the effects of mu opioid agonists on supraoptic (SON)
vasopressin and oxytocin magnocellular neurons by ascertaining the
specific K and Ca conductances affected by mu opioid agonists and
characterize the interaction of estrogen and chronic morphine on SON
neurons.A third series of experiments will investigate the cellular
mechanism by which estrogen and morphine decrease the potency of mu
opioid agonists to hyperpolarize ARC (SON) neurons by measuring the
expression of G-alpha-i and G-alpha-o mRNA using in situ hybridization
and immunocytochemistry to identify the cells. These experiments will
be followed by whole cell patch recording from ARC (SON) neurons to
study the role of G-proteins in the estrogen- mediated attenuation of the
mu opioid response.
Effective start/end date9/30/948/31/00


  • National Institutes of Health: $68,172.00
  • National Institutes of Health: $78,903.00


  • Medicine(all)


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