CA2+ ANTAGONISTS AND BRAIN DOPAMINE RECEPTOR REGULATION

Project: Research project

Project Details

Description

Tardive dyskinesia is a condition produced by long-term
antipsychotic drug use, and affects millions of people world-wide.
Though the problems has been termed a "dopamine supersensitivity
syndrome," this undoubtedly describes only part of the underlying
pathophysiology. Recent clinical evidence, in fact, suggests that
calcium channel inhibitors may be useful for reducing the symptoms
of tardive dyskinesia, as well as the symptoms of some other
neuropsychiatric disorders. The goal of this proposal, therefore,
is to further the understanding of dopamine and calcium related
processes in animal models of human neuro- and psychopathology. Within a three year period, the experiments described in this
proposal will examine the hypothesis that calcium channel
inhibitors exert direct effects on dopamine receptor regulation and
(or) function. Thus, this project will characterize: (1) the
effects of chronic administration of calcium channel inhibitors on
the development and the maintenance of neuroleptic induced changes
in dopamine receptor characteristics and activity, (2) the
interaction in vitro between calcium channel inhibitors, adenylate
cyclase activity, and dopamine receptor characteristics, and (3)
the role of dopamine (lesions) in the effects of calcium channel
inhibitors on dopamine receptor regulation and function. The experiments will characterize i) changes in D1 ((3H)SCH23390)
and D2 ((3H)spiroperidol) receptor recognition site density and
affinity for ligand, ii) agonist displacement of the respective
radioligand in the presence and absence of guanine nucleotide and
iii) changes in D1 receptor mediated activation and D2 receptor
mediated inhibition of adenylate cyclase activity in rat brain
striatum.
StatusFinished
Effective start/end date8/1/887/31/91

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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