Neurons in the dorsomedial hypothalamus (DMH) play key roles in physiological responses to exteroceptive ("emotional") stress in rats, including tachycardia. Tachycardia evoked from the DMH or seen in experimental stress in rats is blocked by microinjection of the GABA(A) receptor agonist muscimol into the rostral raphe pallidus (rRP), an important thermoregulatory site in the brain stem, where disinhibition elicits sympathetically mediated activation of brown adipose tissue (BAT) and cutaneous vasoconstriction in the tail. Disinhibition of neurons in the DMH also elevates core temperature in conscious rats and sympathetic activity to least significant difference interscapular BAT (IBAT) and IBAT temperature in anesthetized preparations. The latter effects are blocked by microinjection of muscimol into the rRP, while microinjection of muscimol into either the rRP or DMH suppresses increases in sympathetic nerve activity to IBAT, IBAT temperature, and core body temperature elicited either by microinjection of PGE(2) into the preoptic area (an experimental model for fever), or central administration of fentanyl. Neurons concentrated in the dorsal region of the DMH project directly to the rRP, a location corresponding to that of neurons trans-synaptically labeled from IBAT. Thus these neurons control nonshivering thermogenesis in rats, and their activation signals its recruitment in diverse experimental paradigms. Evidence also points to a role for neurons in the DMH in thermoregulatory cutaneous vasoconstriction, shivering, and endocrine adjustments. These directions provide intriguing avenues for future exploration that may expand our understanding of the DMH as an important hypothalamic site for the integration of autonomic, endocrine, and behavioral responses to diverse challenges.

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Activation of neurons in the region of the dorsomedial hypothalamus (DMH) appears to generate the sympathetically mediated tachycardia seen in experimental stress in rats. The purpose of this study was to assess the role of neurons in the area of the medullary raphe pallidus (RP) in the tachycardia caused by stimulation of the DMH. The cardiovascular response to microinjection of the GABAA receptor antagonist bicuculline methiodide (BMI) 10 pmol (100 nl)−1 into the DMH was assessed before, and after, injection of the GABAA receptor agonist muscimol 80 pmol (100 nl)−1 or saline vehicle 100 nl into the RP in urethane‐anaesthetized rats. Tachycardia evoked by microinjection of BMI into the DMH was mimicked by microinjection of BMI 30 pmol (75 nl)−1 into the RP. This DMH‐induced tachycardia was markedly suppressed after injection of muscimol into the RP, but the response was unaffected by injection of saline into the same region. Thus, DMH‐induced tachycardia is mediated through activation of neurons in the area of the RP, suggesting that these neurons may play a previously unrecognized role in stress‐induced cardiac stimulation.

Both the dorsomedial hypothalamic nucleus (DMH) and the paraventricular hypothalamic nucleus (PVN) have been implicated in the neural control of the cardiovascular response to stress. We used the GABAA agonist muscimol to inhibit neuronal activation and attempted to identify hypothalamic nuclei required for the cardiovascular response to air stress. Chronically instrumented rats received bilateral injections of either 80 pmol of muscimol or 100 nl of saline vehicle into the DMH, the PVN, or an intermediate area (including the rostral edge of the DMH and the region between the two nuclei) and were placed immediately in a restraining tube and subjected to 20 min of air stress. In all rats, air stress after vehicle injections caused marked increases in heart rate (137 +/- 6 beats/min) and blood pressure (26 +/- 2 mmHg). Microinjection of muscimol into the DMH suppressed the heart rate and blood pressure response by 85 and 68%, respectively. Identical microinjection of muscimol into the intermediate area between the DMH and the PVN attenuated the increases in heart rate by only 46% and in blood pressure by 52%. In contrast, similar injections into the vicinity of the PVN failed to alter the cardiovascular response to air stress. These findings demonstrate that muscimol-induced inhibition of neuronal activity in the region of the DMH blocks air stress-induced increases in heart rate and arterial pressure, whereas similar treatment in the area of the PVN has no effect.

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Disinhibition of neurons in the region of the dorsomedial hypothalamus (DMH) elicits sympathetically mediated tachycardia in rats through activation of the brain stem raphe pallidus (RP), and this same mechanism appears to be largely responsible for the increases in heart rate (HR) seen in air jet stress in this species. Neurons projecting to the RP from the DMH are said to be concentrated in a specific subregion, the dorsal hypothalamic area (DA). Here, we examined the hypothesis that the location of RP-projecting neurons in the DA correspond to the sites at which microinjection of bicuculline methiodide (BMI) evokes the greatest increases in HR. To determine the distribution of RP-projecting neurons in the DA, cholera toxin B was injected in the RP in four rats. A consistent pattern of retrograde labeling was seen in every rat. In the hypothalamus, RP-projecting neurons were most heavily concentrated midway between the mammillothalamic tract and the dorsal tip of the third ventricle dorsal to the dorsomedial hypothalamic nucleus approximately 3.30 mm caudal to bregma. In a second series of experiments, the HR response to microinjections of BMI (2 pmol/5 nl; n = 76) was mapped at sites in the DA and surrounding areas in 22 urethane-anesthetized rats. All injection sites were located from 2.56 to 4.16 mm posterior to bregma, and the microinjections that evoked the largest increase in HR (i.e., >100 beats/min in some instances) were located in a region where RP-projecting neurons were most densely concentrated. Thus RP-projecting neurons in the DA may mediate DMH-induced tachycardia and thus play a role in stress-induced cardiac stimulation.

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.