Abstract

We propose to investigate the direct actions of the narcotic drug LAAM and its two primary metabolites, N-LAAM and DN-LAAM on brain growth in vivo and in culture. The chick embryo will be the experimental animal for the in vivo studies and dissociated brain cell cultures from chick embryos will be the culture system. Specific studies will include: 1. Accumulation and disappearance of 14C-LAAM and its two metabolites in several brain areas of the chick embryo after injection in vivo. 2. The effects of LAAM, N-LAAM and DN-LAAM given at various doses and at various embryonic ages on the development of enzymes associated with growth; ornithine decarboxylase, choline acetyltransferase and tyrosine hydroxylase. 3. The ontological development of opiate receptor binding in several brain areas of the chick and the effects of these narcotic drugs. Using the dissociated brain cell cultures, we will investigate the direct effects of LAAM, N-LAAM and DN-LAAM on morphological growth (neuronal-glial ratio, number and length of neuronal processes, specific neurons affected) and on the maturational profiles of growth enzymes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
3R01HD018894-06S1
Application #
3316058
Study Section
Pharmacology I Research Subcommittee (DABR)
Project Start
1979-08-01
Project End
1987-06-30
Budget Start
1986-12-01
Budget End
1987-06-30
Support Year
6
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Colorado Denver
Department
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045

  Publications

Mangoura, D; Sakellaridis, N; Vernadakis, A (1988) Cholinergic neurons in cultures derived from three-, six- or eight-day-old chick embryo: a biochemical and immunocytochemical study. Brain Res 468:37-46
Vernadakis, A; Mangoura, D A (1988) Factors influencing glia growth in culture: nutrients and cell-secreted factors. Prog Clin Biol Res 259:57-79
Vernadakis, A (1988) Neuron-glia interrelations. Int Rev Neurobiol 30:149-224
Mangoura, D; Vernadakis, A (1988) GABAergic neurons in cultures derived from three-, six- or eight-day-old chick embryo: a biochemical and immunocytochemical study. Brain Res 468:25-35
Mangoura, D; Sakellaridis, N; Vernadakis, A (1988) Factors influencing neuronal growth in primary cultures derived from 3-day-old chick embryos. Int J Dev Neurosci 6:89-102
Geladopoulos, T; Sakellaridis, N; Vernadakis, A (1987) Differential maturation of mu and delta opioid receptors in the chick embryonic brain. Neurochem Res 12:279-88
Sakellaridis, N; Vernadakis, A (1987) The chick embryo vs. neural tissue culture as models for the study of opiate neurotoxicity in development. Prog Clin Biol Res 253:85-100
Sakellaridis, N; Mangoura, D; Vernadakis, A (1986) Effects of opiates on the growth of neuron-enriched cultures from chick embryonic brain. Int J Dev Neurosci 4:293-302
Vernadakis, A; Sakellaridis, N; Mangoura, D (1986) Growth patterns of primary cultures dissociated from 3-day-old chick embryos: morphological and biochemical comparisons. J Neurosci Res 16:397-407
Sakellaridis, N; Mangoura, D; Vernadakis, A (1986) Effects of neuron-conditioned medium and fetal calf serum content on glial growth in dissociated cultures. Brain Res 392:31-41

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