Brattleboro rats exhibit normal Pa co 2-induced changes in cerebral microcirculation

Abstract

Prominent biochemical theories of psychiatry are based on proposed catecholaminergic mechanisms. Furthermore, the central adrenergic system (CAS) has been implicated in various central phenomena (e.g., sleep, memory, motivation) and psychiatric disorders (e.g., affective disorders, schizophrenia). Yet the knowledge of cellular mechanisms involved in mediating these actions remains beyond our understanding. A synthesis of anatomical and physiological research has led to the development of a neurohumoral hypothesis proposing that one function of the CAS is the regulation of the blood-brain barrier as part of an intraaxial autonomic system anatomically distinct from, but having central functions analogous to, those of the peripheral sympathetic system (Hartman et al. 1980). One specific function predicted by this concept is modulation of cerebral microvascular flow and permeability. By regulating cerebral capillary permeability, the CAS-and drugs that act on it-could have profound effects on cerebral fluid dynamics, metabolism, and ultimately, brain function. Moreover, the relationship between the CAS and the cerebral microvasculature can serve as a model in which the effects of a defined neural system on an end-organ within the brain can be quantified in vivo. This relationship represents one of the few examples of a central neuron terminating directly on an end-organ (i.e., the cerebral capillary) instead of on another neuron. Such a model system is of relevance to understanding neuron-end-organ mechanisms and, ultimately, their relationship to psychiatric disorders. We have explored the relationship between the CAS and cerebromicrocirculatory regulation using pharmacological (Preskom et al. 1980, 1982a,b; Kent et al. 1986) and physiological (Raichle et al. 1975; Elam et al. 1981) paradigms, An example of the latter is the inhalation of co*, which induces changes in the cerebromicrocirculation and increases the firing rate of the locus coeruleus (LC) (Kent et al. 1986). A remaining question is whether the CO*-induced release of norepinephrine (NE) from the LC affects the microvasculature directly or not.