The properties and functions of dopamine (DA) neurons that comprise the tuberoinfundibular (TI) system are markedly different from those """"""""typical"""""""" DA neurons play important roles in maintaining motor (nigrostriatal DA neurons) and basic psychic (mesolimbic- mesocortical DA neurons) functions, whereas TIDA neurons regulate the release of prolactin from the anterior pituitary. In turn, TIDA but not mesotelencephalic DA neurons are tonically activated by prolactin. Recent evidence indicates that TIDA neurons are also regulated by afferent neuronal systems that are activated by suckling and stress. Currently available drugs that facilitate or block DA transmission processes are non-selective in that they affect all DA neuronal systems and can, therefore, cause disturbing motor, psychic and endocrinological side effects. Knowledge of how different DA neuronal systems are regulated should facilitate the development of new drugs that selectively influence the activity or function of one DA neuronal system without altering the others. The long-term objective of this project is to characterize endocrinological and neuronal factors that influence TIDA neurons. The activity of these neurons will be monitored by measuring: 1) the concentration of dihydroxyphenylacetic acid (DOPAC), a major metabolite of DA, and the rates of synthesis and turnover of DA in brain regions that contain the cell bodies (arcuate nucleus) and terminals (median eminence) of these neurons, and 2) the plasma concentrations of prolactin. These measurements will be made following manipulations that alter the functional activities of afferent neuronal systems which project to and regulate TIDA neurons. These manipulations will include activation (electrical stimulation) or destruction (knife cuts or electrolytic lesions) of discrete brain regions that could contain cell bodies or axons of afferent neurons. In this way the distribution and chemical characteristics of neurons that increase (excitatory afferents) or decrease (inhibitory afferents) the activity of TIDA neurons will be determined. The lesions studies will also assist in determining if pharmacological-endocrinological manipulations (e.g., administration of prolactin) and physiological stimuli (e.g., restraint stress) alter the activity of TIDA neurons via afferent neuronal projections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
4R37MH042802-27
Application #
3486871
Study Section
Special Emphasis Panel (NSS)
Project Start
1978-09-01
Project End
1998-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
27
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Michigan State University
Department
Type
Schools of Medicine
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Hentschel, K; Moore, K E; Lookingland, K J (2000) Effects of prolactin on expression of Fos-related antigens in tyrosine hydroxylase-immunoreactive neurons in subdivisions of the arcuate nucleus. Brain Res 857:110-8
Hentschel, K; Fleckenstein, A E; Toney, T W et al. (2000) Prolactin regulation of tuberoinfundibular dopaminergic neurons: immunoneutralization studies. Brain Res 852:28-36
Hentschel, K; Cheung, S; Moore, K E et al. (1998) Pharmacological evidence that neurotensin mediates prolactin-induced activation of tuberoinfundibular dopamine neurons. Neuroendocrinology 68:71-6
Durham, R A; Johnson, J D; Eaton, M J et al. (1998) Opposing roles for dopamine D1 and D2 receptors in the regulation of hypothalamic tuberoinfundibular dopamine neurons. Eur J Pharmacol 355:141-7
Durham, R A; Eaton, M J; Moore, K E et al. (1997) Effects of selective activation of dopamine D2 and D3 receptors on prolactin secretion and the activity of tuberoinfundibular dopamine neurons. Eur J Pharmacol 335:37-42
Eaton, M J; Lookingland, K J; Moore, K E (1996) The sigma receptor ligand rimcazole alters secretion of prolactin and alpha-melanocyte stimulating hormone by dopaminergic and non-dopaminergic mechanisms. Eur J Pharmacol 299:171-7
Durham, R A; Johnson, J D; Moore, K E et al. (1996) Evidence that D2 receptor-mediated activation of hypothalamic tuberoinfundibular dopaminergic neurons in the male rat occurs via inhibition of tonically active afferent dynorphinergic neurons. Brain Res 732:113-20
Krajnak, K; Lookingland, K J; Nunez, A A (1995) Seasonal changes in median eminence dopamine in male Syrian hamsters: role of the gonads and duration of exposure to short days. Brain Res Bull 37:617-22
Wagner, E J; Moore, K E; Lookingland, K J (1994) Neurochemical evidence that AMPA receptor-mediated tonic inhibition of hypothalamic dopaminergic neurons occurs via activation of inhibitory interneurons. Brain Res 660:319-22
Wagner, E J; Moore, K E; Lookingland, K J (1994) Non-NMDA receptor-mediated regulation of hypothalamic dopaminergic neurons in the rat. Eur J Pharmacol 254:105-12

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