Abstract

The neuropeptides are a class of substances recently isolated from neural tissue and have been found to influence the activity of the nervous system at the level of the membrane, the neuron and the behaving organism. Immunohistochemistry of these substances has revealed discrete and rather extensive neuropeptide immunoreactivity in neuronal perikarya, axons and terminals. This proposal focuses on determining the details of the differential distribution of two of these peptides --methionine- and leucine-enkephalin. In addition to the extensiveness of enkephalinergic systems revealed in our preliminary studies, the enkephalins are of interist in light of their morphinomimetic properties at opiate receptors as well as on an organismic level. This proposal seeks to determine the differential distribution of enkephalins by purifying antisera to mono-specificity for each enkephalin by removing cross-reacting antibodies on a heterologous immunoabsorbent. The purified, monospecific antisera to each enkephalin will then be used in immunofluorescence histochemical procedures on sections of the rat brain to reveal the terminals, axons and perikarya containing either methionine- or leucine-enkephalin immunoreactivity. The results of these studies will be translated into detailed, schematic coronal maps of the rat brain with approximate stereotaxic coordinates. The connectivity of selected perikarya and terminals will be studied with immunofluorescence histochemistry on rat brains after stereotaxic lesions of enkephalinergic perikarya. Disappearance of normally-fluorescent terminals will indicate the perikarya of origin for these terminals. Selected regions will also be studied with antisera to other neuropeptides where convergence of enkephalinergic and other peptidergic systems has been reported. Finally, a small portion of this proposal (10%) aims to investigate possible changes in the differential distribution of the enkephalins in selected nuclei in the brains of mice made tolerant to and dependent upon opiates.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA002148-09
Application #
3207143
Study Section
(SRC)
Project Start
1978-09-30
Project End
1988-11-30
Budget Start
1987-01-01
Budget End
1987-11-30
Support Year
9
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Tallaksen-Greene, S J; Elde, R; Wessendorf, M W (1993) Regional distribution of serotonin and substance P co-existing in nerve fibers and terminals in the brainstem of the rat. Neuroscience 53:1127-42
Wetmore, C; Elde, R (1991) Detection and characterization of a sensory microganglion associated with the spinal accessory nerve: a scanning laser confocal microscopic study of the neurons and their processes. J Comp Neurol 305:148-63
Lacey, C B; Elde, R P; Seybold, V S (1991) Localization of vasoactive intestinal peptide binding sites in the thymus and bursa of Fabricius of the chick. Peptides 12:383-91
Hill, E L; Elde, R (1991) Distribution of CGRP-, VIP-, D beta H-, SP-, and NPY-immunoreactive nerves in the periosteum of the rat. Cell Tissue Res 264:469-80
Hill, E L; Turner, R; Elde, R (1991) Effects of neonatal sympathectomy and capsaicin treatment on bone remodeling in rats. Neuroscience 44:747-55
Stevens, C W; Lacey, C B; Miller, K E et al. (1991) Biochemical characterization and regional quantification of mu, delta and kappa opioid binding sites in rat spinal cord. Brain Res 550:77-85
Burstein, R; Cliffer, K D; Giesler Jr, G J (1990) Cells of origin of the spinohypothalamic tract in the rat. J Comp Neurol 291:329-44
Burstein, R; Wang, J L; Elde, R P et al. (1990) Neurons in the sacral parasympathetic nucleus that project to the hypothalamus do not also project through the pelvic nerve--a double labeling study combining Fluoro-gold and cholera toxin B in the rat. Brain Res 506:159-65
Cliffer, K D; Urca, G; Elde, R P et al. (1988) Studies of peptidergic input to the lateral spinal nucleus. Brain Res 460:356-60
Appel, N M; Elde, R P (1988) The intermediolateral cell column of the thoracic spinal cord is comprised of target-specific subnuclei: evidence from retrograde transport studies and immunohistochemistry. J Neurosci 8:1767-75

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