Abstract

In the laboratory, work will be addressed to three endogenous neuropeptides, oxytocin (OXY), neurotensin (NT) and thyrotropin-releasing hormone (TRH). Work with OXY will focus on the property of this peptide to produce maternal behavior in virgin female rats. Interest is now focused on blocking the action of endogenous OXY in triggering this behavior in a variety of circumstances. Neurotensin is of interest because many of its actions run parallel to those of neuroleptic drugs. We propose to identify the sites in brain where NT enhances pentobarbital-induced sleeping time and where it enhances pentobarbital-induced hypothermia. Additional studies bear upon the role of NT in thermoregulation. While NT prolongs pentobarbital-induced sleeping time, TRH shortens it. We will use this property of TRH to study the action of putative inhibitors of TRH synthesis and inhibitors of TRH degradation. Additional studies are addressed to probable interactions between TRH and NT. In the clinic, work will focus on three endogenous peptides: NT, TRH, and insulin. Because NT can blunt the TSH response to TRH it will be of interest to discern whether patients with blunted responses have altered levels of NT in spinal fluid. The TSH response to TRH will also be studied as regards its characteristics in a large population of normals and its possible influence by stage of the menstrual cycle. Its possible value in predicting the efficacy of L-triiodothyronine as an adjunct to imipramine in depression will also be studied. The behavioral and endocrine effects of insulin will be studied in normal subjects and schizophrenic patients while hypoglycemia is prevented by glucose administration. These studies are prompted in part by recent observations that not all endocrine effects of insulin are due to hypoglycemia. This broad program of research into the behavioral and predictive properties of peptide hormones in both animals and man will involve a variety of techniques and a number of collaborators skilled in their special application.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Award (K05)
Project #
5K05MH022536-18
Application #
3076053
Study Section
Research Scientist Development Review Committee (MHK)
Project Start
1985-07-01
Project End
1990-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
18
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Mason, G A; Walker, C H; Prange Jr, A J (1993) L-triiodothyronine: is this peripheral hormone a central neurotransmitter? Neuropsychopharmacology 8:253-8
Prange Jr, A J (1992) The manifold actions of neurotensin, a trophotropic agent. Ann N Y Acad Sci 668:298-306
Garbutt, J C; Mayo Jr, J P; Mason, G A et al. (1991) Interpretation of the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH): implications of an improved TSH assay system. Biol Psychiatry 29:718-20
Hashimoto, H; Walker, C H; Prange Jr, A J et al. (1991) The effects of thyroid hormones on potassium-stimulated release of 3H-GABA by synaptosomes of rat cerebral cortex. Neuropsychopharmacology 5:49-54
Stern, R A; Nevels, C T; Shelhorse, M E et al. (1991) Antidepressant and memory effects of combined thyroid hormone treatment and electroconvulsive therapy: preliminary findings. Biol Psychiatry 30:623-7
Shimoda, K; Mason, G A; Walker, C H et al. (1991) Administration of chlordiazepoxide affects [3H][3-MeHis2]thyrotropin-releasing hormone binding in rat brain. Peptides 12:199-202
Mason, G A; Walker, C H; Prange Jr, A J (1990) Depolarization-dependent 45Ca uptake by synaptosomes of rat cerebral cortex is enhanced by L-triiodothyronine. Neuropsychopharmacology 3:291-5
Mason, G A; Stanley, D A; Walker, C H et al. (1988) Chronic alcohol ingestion decreases pituitary-thyroid axis measures in Fischer-344 rats. Alcohol Clin Exp Res 12:731-4
Pedersen, C A; Caldwell, J D; Drago, F et al. (1988) Grooming behavioral effects of oxytocin. Pharmacology, ontogeny, and comparisons with other nonapeptides. Ann N Y Acad Sci 525:245-56
Mason, G A; Bondy, S C; Nemeroff, C B et al. (1987) The effects of thyroid state on beta-adrenergic and serotonergic receptors in rat brain. Psychoneuroendocrinology 12:261-70

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