Peripheral, autonomic regulation of locus coeruleus noradrenergic neurons in brain: putative implications for psychiatry and psychopharmacology

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Abstract
In 1946 von Euler identified the major transmitter of sympathetic nerve fibers, norepinephrine (NE), and about a decade later Vogt (1954) provided the first evidence that NE may also serve as a neurotransmitter in the central nervous system (CNS). Since that time, a literal explosion in CNS neurotransmitter research has taken place involving histological, biochemical, physiological, pharmacological and clinical investigations, Yet, it is only now that we are beginning to understand the biological function of NE in brain, in particular because of recent advances regarding the physiology and regulation of NE neurons in locus coeruleus (LC), a bilateral pontine structure with a uniquely wide-spread terminal network reaching throughout the neuroaxis and in primates accounting for about 70% of all brain NE. Recently, the neurobiology of the LC noradrenergic network was extensively reviewed by Foote et al. (1983), and its implication in vigilance as well as global orientation of behavior towards imperative, environmental sensory stimuli was outlined. Yet, more recent information regarding the peripheral, autonomic regulation of LC neurons in brain provides fundamentally new biological aspects on behavior and mental function which seem to allow a more integrated view of the rôle of brain NE in the overall function of the individual than previously understood. The purpose of this review is to summarize these findings and, furthermore, to outline some putative implications for psychiatry and neuropsychopharmacology. In particular, the new data seem to allow a better understanding of how autonomic vulnerability or visceral dysfunction may precipitate or aggravate mental symptoms and disorder.