This research proposal intends to elucidate the specific morphological substrate demonstrating the postsynaptic site of adenylate cyclase-linked mediation of dopaminergic neurotransmission in the rat caudate nucleus. The dopamine receptor subtype subserving cyclic AMP production has been termed the D1 receptor class. Utilization of histochemical techniques for in vitro receptor binding and immunohistochemistry cyclic AMP allows chemical determination of the element(s) mediating the response of this dopamine receptor subtype in highly organized tissue having multiple cell types. This approach will also allow correlation with other chemically defined cell populations of the caudate nucleus by neurotransmitter content, e.g., acetylcholinergic, GABAergic, substance P-containing, enkephalinergic, and somatostatin-containing. The receptor ligand-immunohistochemically characterized cell populations can be further correlated with their efferent destination through use of retrograde dye transport techniques. The ultrastructural study of synaptic relationships of the D1 dopamine receptor/cyclic AMP-containing cells will also be investigated. We plan to examine three experimental animal groups to demonstrate cellular changes which occur between 1) normal D1 receptor localization patterns, 2) the Parkinson-like, dopamine-lacking caudate nucleus, and 3) the dopamine-supplemented, nigrostriatal-lesioned rat. These investigations should further our understanding of dopaminergic mechanisms utilizing cyclic AMP second messenger systems in normal and neurochemically compromised states.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS023079-03
Application #
3406157
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1986-02-01
Project End
1990-01-31
Budget Start
1988-02-01
Budget End
1989-01-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Vermont & St Agric College
Department
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
Ariano, M A; Drago, J; Sibley, D R et al. (1998) Striatal excitatory amino acid receptor subunit expression in the D1A-dopamine receptor-deficient mouse. Dev Neurosci 20:237-41
Ariano, M A; Larson, E R; Noblett, K L et al. (1997) Coexpression of striatal dopamine receptor subtypes and excitatory amino acid subunits. Synapse 26:400-14
Mathiasen, J R; Larson, E R; Ariano, M A et al. (1996) Neurophysin expression is stimulated by dopamine D1 agonist in dispersed hypothalamic cultures. Am J Physiol 270:R404-12
Larson, E R; Ariano, M A (1995) D3 and D2 dopamine receptors: visualization of cellular expression patterns in motor and limbic structures. Synapse 20:325-37
Larson, E R; Ariano, M A (1994) Dopamine receptor binding on identified striatonigral neurons. Neurosci Lett 172:101-6
Ariano, M A; Sibley, D R (1994) Dopamine receptor distribution in the rat CNS: elucidation using anti-peptide antisera directed against D1A and D3 subtypes. Brain Res 649:95-110
Fisher, R S; Levine, M S; Sibley, D R et al. (1994) D2 dopamine receptor protein location: Golgi impregnation-gold toned and ultrastructural analysis of the rat neostriatum. J Neurosci Res 38:551-64
Ariano, M A; Fisher, R S; Smyk-Randall, E et al. (1993) D2 dopamine receptor distribution in the rodent CNS using anti-peptide antisera. Brain Res 609:71-80
Wagner, H J; Luo, B G; Ariano, M A et al. (1993) Localization of D2 dopamine receptors in vertebrate retinae with anti-peptide antibodies. J Comp Neurol 331:469-81
Ariano, M A; Engber, T M; Susel, Z et al. (1991) Striatal D1 dopamine receptor morphochemistry following continuous or intermittent L-dopa replacement therapy. Exp Neurol 112:112-8

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