Abstract

The morphological changes which accompany development of the nervous system have been well characterized. In contrast, the neurochemical and molecular events which underlie these processes are less well understood. We propose to utilize a combination of neuroanatomical and biochemical techniques to elucidate several aspects of the functional role of opioid systems during development of the CNS. The differential developmental appearance of opioid receptor subtypes will be characterized, and will be correlated with the appearance of specific opioid peptide systems. The pharma-ological characteristics of these early receptors will be analyzed and compared to those of the adult. The hypothesis that Mu and Delta receptor subtypes represent intercoverting forms of the same receptor will also be examined in detail. Well characterized behavioral and neuroendocrine deficits have been shown to result from prenatal exposure to morphine. We propose to analyze the molecular basis of these deficits, by comparing several aspects of hypothalamic organization in normal and drug-treated animals. This analysis should provide data relevant to the hypothesis that opioid receptors are important in guidance of neuronal migration.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019319-03
Application #
3399349
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1983-04-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1987-03-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of California Irvine
Department
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697

  Publications

Winzer-Serhan, Ursula H; Chen, Yiling; Leslie, Frances M (2003) Expression of opioid peptides and receptors in striatum and substantia nigra during rat brain development. J Chem Neuroanat 26:17-36
Leslie, F M; Chen, Y; Winzer-Serhan, U H (1998) Opioid receptor and peptide mRNA expression in proliferative zones of fetal rat central nervous system. Can J Physiol Pharmacol 76:284-93
Kitchen, I; Leslie, F M; Kelly, M et al. (1995) Development of delta-opioid receptor subtypes and the regulatory role of weaning: radioligand binding, autoradiography and in situ hybridization studies. J Pharmacol Exp Ther 275:1597-607
Raymon, H K; Leslie, F M (1994) Opioid effects on [3H]norepinephrine release from dissociated embryonic locus coeruleus cell cultures. J Neurochem 62:1015-24
Smith, J A; Leslie, F M; Broide, R S et al. (1993) Long-term changes in striatal opioid systems after 6-hydroxydopamine lesion of rat substantia nigra. Neuroscience 55:935-51
Raymon, H K; Smith, T D; Leslie, F M (1992) Further pharmacological characterization of [3H]idazoxan binding sites in rat brain: evidence for predominant labeling of alpha 2-adrenergic receptors. Brain Res 582:261-7
Smith, J A; Loughlin, S E; Leslie, F M (1992) kappa-Opioid inhibition of [3H]dopamine release from rat ventral mesencephalic dissociated cell cultures. Mol Pharmacol 42:575-83
Loughlin, S E; An, A; Leslie, F M (1992) Opioid receptor changes in weaver mouse striatum. Brain Res 585:149-55
Arnsten, A F; Leslie, F M (1991) Behavioral and receptor binding analysis of the alpha 2-adrenergic agonist, 5-bromo-6 [2-imidazoline-2-yl amino] quinoxaline (UK-14304): evidence for cognitive enhancement at an alpha 2-adrenoceptor subtype. Neuropharmacology 30:1279-89
Loughlin, S E; Kornblum, H I; Massamiri, T et al. (1991) Transient appearance of beta-endorphin immunoreactive cells within the germinal zone of neonatal rat forebrain. Int J Dev Neurosci 9:493-500

Showing the most recent 10 out of 22 publications