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.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Method to Extend Research in Time (MERIT) Award (R37)
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Special Emphasis Panel (NSS)
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Michigan State University
Schools of Medicine
East Lansing
United States
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