Sympathetically mediated tachycardia is a characteristic feature of the physiological response to emotional or psychological stress in mammals. Activation of neurons in the region of the dorsomedial hypothalamus appears to play a key role in the integration of this response. Tachycardia evoked by chemical stimulation of the dorsomedial hypothalamus can be suppressed by microinjection of the GABAA receptor agonist and neuronal inhibitor muscimol into the raphe pallidus (RP). Therefore, we tested the hypothesis that neuronal excitation in the RP mediates tachycardia seen in experimental air stress in rats. Microinjection of the GABAA receptor antagonist bicuculline methiodide (BMI) into the RP evoked increases in heart rate. At the same sites, microinjection of muscimol (80 pmol (100 nl)−1) had no effect on heart rate under baseline conditions but virtually abolished air stress‐induced tachycardia, while microinjection of lower doses (10 or 20 pmol) produced transient but clear suppression. Microinjection of muscimol at sites outside the RP had no effect on stress‐induced tachycardia, although modest suppression was apparent after injection at two sites within 500 μm of the RP. In another series of experiments, microinjection of muscimol (80 pmol (100 nl)−1) into the RP failed to influence the changes in heart rate produced by baroreceptor loading or unloading. These findings indicate that activity of neurons in the RP plays a previously unrecognized role in the generation of stress‐induced tachycardia.
Zaretsky, Dmitry V., Maria V. Zaretskaia, and Joseph A. DiMicco. Stimulation and blockade of GABAA receptors in the raphe pallidus: effects on body temperature, heart rate, and blood pressure in conscious rats. Am J Physiol Regul Integr Comp Physiol 285: R110-R116, 2003. First published February 27, 2003 10.1152/ajpregu.00016. 2003.-Studies in anesthetized rats have implicated GABA A receptors in the region of the medullary raphe pallidus (RP) at the level of the facial nucleus in sympathetic nervous regulation of both heart rate and thermoregulatory mechanisms. Therefore, we examined the effect of microinjection of muscimol, a GABAA receptor agonist, and of bicuculline methiodide (BMI), a GABAA receptor antagonist, into the same region of the RP on heart rate, blood pressure, and core body temperature in conscious rats. Microinjection of BMI (40 pmol) into the RP evoked tachycardia that appeared within 1 min and was maximal within 10 min but had little or no effect on blood pressure or body temperature. Microinjection of muscimol (10-80 pmol) at the same sites in the RP evoked marked dose-related decreases in body temperature that developed more slowly (i.e., maximum decreases appearing at 60-75 min after 80 pmol) but had no effect on heart rate or blood pressure. Injection of either agent at sites outside the region had lesser or no effect on the measured parameters. These findings suggest that activity of neurons in the region of the RP plays an important role in the maintenance of body temperature but not heart rate under baseline conditions in conscious rats. Specifically, thermoregulatory neurons in this region appear to be tonically active and contribute to maintenance of body temperature under baseline conditions, while cardiac sympathetic premotor neurons in the RP are not active under these circumstances and thus do not support basal heart rate in conscious rats. raphe nuclei; conscious rat; heart rate; blood pressure; body temperature MAINTENANCE OF BODY TEMPERATURE in a relatively narrow range is an important homeostatic function that is closely regulated by the brain. The role of the hypothalamus in this process has long been acknowledged, although the specific mechanisms and efferent central pathways through which the hypothalamus acts to control core body temperature are not currently known. In the rat, one region containing neurons that both receive input from hypothalamic areas known to influence thermoregulatory mechanisms and project to neurons thought to control those mechanisms is the raphe pallidus (RP) in the medulla. Neurons in the region of the RP in the rat medulla appear to be capable of influencing sympathetic modulation of cardiovascular function and/or thermoregulatory mechanisms. In anesthetized rats, microinjection of the GABA A receptor antagonist bicuculline methiodide (BMI) into this area has been reported to increase sympathetic nerve activity to brown fat and to produce cutaneous vasoconstriction in the tail (3,8,12) or to block the cutaneous vasodilation in the tail resul...
Neurons in the rostral raphe pallidus (rRP) have been proposed to mediate experimental stress-induced tachycardia and fever in rats, and projections from the dorsomedial hypothalamus (DMH) may signal their activation in these settings. Thus, we examined c-fos expression evoked by air jet/restraint stress and restraint stress or by systemic administration of lipopolysaccharide (10 microg/kg and 100 microg/kg) as well as the distribution of the neuronal nitric oxide synthase (nNOS) in neurons retrogradely labeled from the raphe with cholera toxin B in key hypothalamic regions. Many neurons in the medial preoptic area and the dorsal area of the DMH were retrogradely labeled, and approximately half of those in the medial preoptic area and moderate numbers in the dorsal DMH were also positive for nNOS. Either stress paradigm or dose of lipopolysaccharide increased the number of c-fos-positive neurons and nNOS/c-fos double-labeled neurons in all regions examined. However, retrogradely labeled neurons positive for c-fos were increased only in the dorsal DMH and adjoining region in both stressed and lipopolysaccharide-treated groups, and triple-labeled neurons were found only in this area in rats subjected to either stress paradigm. Thus, hypothalamic neurons that project to the rRP and express c-fos in response to either experimental stress or systemic inflammation are found only in the dorsal DMH, and many of those activated by stress contain nNOS, suggesting that nitric oxide may play a role in signaling in this pathway.
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