Abstract

We plan to continue, as well as to initiate research in the following areas: (1) To study the dopamine (DA) receptors at the molecular level. The solubilized striatal DA receptors will be further purified and characterized. The purified antigens will be used for production of specific monoclonal and/or polyclonal antibodies. (2) The turnover rates of normosensitive, subsensitive and supersensitive striatal DA receptor subtypes will be studied. The recovery rates of the functional DA receptors will be assessed by behavioral and biochemical tests. (3) The effects of selective and non-selective DA agonists on extrapyramidal dysfunctions in monkeys with unilateral ventromedial tegmental lesions of the brain stem and in NMPTP-treated monkeys will be investigated. The biochemical, histochemical and neurological deficits in the two non-human primate models which mimic Parkinson's disease will be studied. (4) The interactions of DA agonists with pre- and postsynaptic (normosensitive and supersensitive) DA receptor subtypes will be evaluated. (5) The involvement of the dopaminergic neuronal system in the compulsive self-mutilative biting behavior will be studied in rats and monkeys with supersensitive DA receptors. The role of DA and of other neurotransmitters in the neuropathology of Lesch-Nyhan syndrome will be investigated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS006801-20
Application #
3393505
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1977-08-01
Project End
1990-11-30
Budget Start
1986-09-01
Budget End
1987-11-30
Support Year
20
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
New York University
Department
Type
Schools of Medicine
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012

  Publications

Janson, A M; Fuxe, K; Goldstein, M et al. (1991) Hypertrophy of dopamine neurons in the primate following ventromedial mesencephalic tegmentum lesion. Exp Brain Res 87:232-8
Harada, K; Meller, E; Goldstein, M (1990) Effects of pertussis toxin on inhibition of synaptosomal tyrosine hydroxylase activity by apomorphine. Eur J Pharmacol 188:123-8
Deutch, A Y; Elsworth, J D; Roth, R H et al. (1990) 3-Acetylpyridine results in degeneration of the extrapyramidal and cerebellar motor systems: loss of the dorsolateral striatal dopamine innervation. Brain Res 527:96-102
Goldstein, M (1989) Monkeys with unilateral ventromedial tegmental lesions of the brain stem: models for Parkinson's disease and Lesch-Nyhan syndrome. Prog Neuropsychopharmacol Biol Psychiatry 13:311-8
Goldstein, M; Lieberman, A N; Helmer, E et al. (1988) Biochemical analysis of caudate nucleus biopsy samples from parkinsonian patients. Ann Neurol 24:685-8
Yokoo, H; Goldstein, M; Meller, E (1988) Receptor reserve at striatal dopamine receptors modulating the release of [3H]dopamine. Eur J Pharmacol 155:323-7
Foster, G A; Schultzberg, M; Kokfelt, T et al. (1988) Ontogeny of the dopamine and cyclic adenosine-3':5'-monophosphate-regulated phosphoprotein (DARPP-32) in the pre- and postnatal mouse central nervous system. Int J Dev Neurosci 6:367-86
Hokfelt, T; Foster, G; Schultzberg, M et al. (1988) DARPP-32 as a marker for D-1 dopaminoceptive cells in the rat brain: prenatal development and presence in glial elements (tanycytes) in the basal hypothalamus. Adv Exp Med Biol 235:65-82
Foster, G A; Schultzberg, M; Hokfelt, T et al. (1987) Development of a dopamine- and cyclic adenosine 3':5'-monophosphate-regulated phosphoprotein (DARPP-32) in the prenatal rat central nervous system, and its relationship to the arrival of presumptive dopaminergic innervation. J Neurosci 7:1994-2018
Adler, C H; Meller, E; Goldstein, M (1987) Receptor reserve at the alpha-2 adrenergic receptor in the rat cerebral cortex. J Pharmacol Exp Ther 240:508-15

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