MEASUREMENT OF BRAIN RECEPTOR FUNCTION IN VIVO

本研究的目的是进一步调查

The objective of the proposed research is to further investigate a new biochemical technique for measuring the activity of brain beta adrenergic receptors in vivo in awake, behaving animals so as to facilitate future research on the role of the central noradrenergic system in behavioral disorders. The technique is based on the collection by microdialysis of the second messenger, cyclic AMP (cAMP), which is formed in the brain in response to beta receptor activation. The central noradrenergic system is known to be an integrative system which appears to play an important role in the regulation of responses to stress and also in the mechanism of action of various antidepressant drugs. Research on the function of this system, however, has been hampered by the lack of a suitable biochemical technique for measuring the function of its postsynaptic receptors in vivo in the brains of awake animals. Recent studies in our laboratory, however, have indicated that a new technique involving intracerebral microdialysis may enable one to obtain a biochemical measure of the activity of these receptors in the rat brain. We have found in preliminary studies using implanted microdialysis probes that increases in cAMP efflux reflecting the activation of brain noradrenergic receptors can be detected in response to intracerebral infusions of norepinephrine. The aim of the proposed research is to follow up these preliminary findings and determine under what conditions the new technique is effective in studying these receptors. This will be accomplished by measuring in vivo cAMP responses to various treatments that cause activation of beta receptors by both exogenous and endogenous norepinephrine. In order to determine if the technique can be used to study the relationship between presynaptic neurotransmitter release and receptor activation simultaneous assays of norepinephrine release and cAMP efflux will be attempted. The proposed research can therefore provide a new and powerful tool for studying how neurotransmission in the central noradrenergic system and other cAMP-linked systems is altered by processes such as adaptation to stress and antidepressant drugs which are involved in the etiology and treatment of psychiatric disorders.