Project: Research project

Project Details


Studies indicate that the neurotransmitter dopamine (DA)
interacts with the enkephalin (ENK, e.g. Met5-enkephalin) and
tachykinin (TAK, e.g. substance P) containing peptidergic neurons
of the basal ganglia. For example, DA receptor blockade or lesion
of nigrostriatal DA neurons leads to enhance ENK and decreased
TAK concentrations in the basal ganglia and/or substantia nigra.
However, the precise nature of development and long-term
plasticity in these peptidergic systems during DA deficiency is
unclear, partly because of the paucity of information concerning
their biosynthetic processes (e.g. transcription, translation and
peptide formation). An elucidation of DA-ENK/TAK relationship
is important, since a deficiency of DA is implicated to the
movement disorders associated with Parkinsonism and Lesch-
Nyhan disease. The working hypothesis is that the development
and maintenance of peptide biosynthesis in the striatopallidal
ENK and striatonigral TAK neurons is under a regulatory control
of nigrostriatal DA and that events that alter the activity of DA
neurons will also modify the biosynthesis. The neurotoxin, 6-
hydroxydopamine induced DA deficiency in rat during an early
postnatal period will be used as a model to study DA-ENK/TAK
relationship. The status of the peptidergic neurons will be
assessed in terms of the rate of transcription of preproenkephalin
and preprotachykinin genes by transcription run-on assays, the
abundance of specific mRNAs by molecular hybridization, the
concentrations of certain precursor and peptides by
radioimmunoassays. DA, 5-hydroxytryptamine and their
metabolites will also be assayed. This proposal will address the
following specific questions: a) What are the molecular events
involved in the postnatal development and biosynthesis of ENK
and TAK peptides? b) Does neonatally induced DA deficiency
lead to enhanced ENK and retarded TAK biosynthesis; if so, at
what period in development does this occur? c) Will
replenishment of the deficit transmitter DA, or treatment with
selective DA receptor (D1 or D2) agonists or peptide (TAK) or
opioid antagonist at the appropriate development period reverse
or modify the peptidergic and certain behavioral alterations
associated with DA deficiency? d) How does the destruction of
serotonergic terminals which are known to proliferate in the
striatum following neonatal DA deficiency affect the peptidergic
neurons? The results obtained will be highly relevant to further
understanding of neurobiologic basis of basal ganglia function.
Effective start/end date4/1/883/31/94


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $84,452.00


  • Medicine(all)
  • Neuroscience(all)


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