Role of the dorsomedial hypothalamus in thermogenesis and tachycardia caused by microinjection of prostaglandin E2 into the preoptic area in anesthetized rats

Zaretskaia, Maria V.; Zaretsky, Dmitry V.; DiMicco, Joseph A.

doi:10.1016/s0304-3940(03)00047-8

Cited by 79 publications

(83 citation statements)

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“…13,14 The central pathway mediating cold-induced cutaneous vasoconstriction may also include a synapse in the DMH. 11 Thus, together, the present and previous observations suggest the possibility that all sympathetically mediated cardiovascular and noncardiovascular responses that are mediated by neurons within the DMH can be powerfully suppressed by activation of central 5-HT 1A receptors.…”

Section: Horiuchi Et Al Dmh Cardiovascular Response and 5-ht 1a Recepmentioning

confidence: 99%

“…12 In addition, bilateral injections of muscimol or kynurenate into the DMH greatly reduces the thermogenic and cardiovascular components of the febrile response generated by injection of prostaglandin E 2 (PGE 2 ) into the preoptic area of the hypothalamus. 13,14 Thus, the DMH appears to be a component of the central pathways mediating the sympathetic changes accompanying fever, as well as those evoked by psychological stress.The descending pathways that mediate the different components of the sympathetic response evoked by activation of the DMH have been shown to include synapses in the rostral ventrolateral medulla (RVLM) and in the region of the raphe pallidus (RPa) in the rostral midline medulla. In particular, the increase in RSNA evoked from the DMH is largely…”

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Activation of 5-Hydroxytryptamine 1A Receptors Suppresses the Cardiovascular Response Evoked From the Dorsomedial Hypothalamic Nucleus

2005

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Abstract-The dorsomedial hypothalamic nucleus is a key component of the central pathways subserving the cardiovascular response to psychological stress, which is believed to be an important risk factor for hypertension. Previous studies indicate that 5-hydroxytryptamine 1A receptors can modulate the cardiovascular responses associated with stress. In this study, we determined in anesthetized rats the effects of systemic or intracisternal administration of 8-hydroxy-2-(di-npropylamino)tetralin, a selective agonist of 5-hydroxytryptamine 1A receptors, and then subsequent administration of the selective antagonist WAY-100635 on the cardiovascular response evoked by activation of the dorsomedial hypothalamic nucleus (by microinjection of bicuculline). The increase in mean arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA) evoked by bicuculline injection into the dorsomedial hypothalamic nucleus was greatly reduced (by 80% to 90%) by administration of 8-hydroxy-2-(di-n-propylamino)tetralin and then completely restored by subsequent administration of WAY-100635, whether administered systemically or intracisternally. In contrast, systemic administration of 8-hydroxy-2-(di-n-propylamino)tetralin had no significant effect on the baseline level or reflex changes in RSNA evoked by chemoreceptor or baroreceptor stimulation and resulted in only a modest reduction ( Key Words: Ⅲ hypothalamus Ⅲ stress Ⅲ baroreflex Ⅲ chemoreceptors P sychological stress is believed to be an important risk factor for hypertension and other cardiovascular disorders. 1 Studies in conscious and anesthetized rats have demonstrated that the dorsomedial hypothalamic nucleus (DMH) plays a critical role in mediating the autonomic, neuroendocrine, and behavioral response to psychological stress, such as air jet stress. 2 Activation of neurons in the DMH evokes anxiety-like behavior associated with a wide range of autonomic and hormonal responses, including increases in heart rate (HR; mediated via an increase in cardiac sympathetic nerve activity 3,4 ), renal sympathetic nerve activity (RSNA), gastrointestinal motility, and in the secretion of adrenomedullary hormones and adrenocorticotropic hormone (corticotropin [ACTH]). 2-8 Conversely, bilateral microinjections into the DMH of muscimol (a ␥-aminobutyric acid type A [GABA A ] receptor agonist) or of kynunerate (an antagonist of ionotropic glutamate receptors) greatly reduces the increases in arterial pressure, HR, ACTH secretion, and anxiety-like behavior normally evoked by air jet stress. 8 -10 It has been shown recently that the DMH also plays an important role in generating thermoregulatory responses.Activation of neurons in the DMH evokes an increase in the activity of sympathetic nerves innervating brown adipose tissue (BAT), accompanied by increases in BAT temperature and end-tidal CO 2 , 3 as well as cutaneous vasoconstriction. 11 These thermoregulatory effects may also be part of a stress response because an increase in body temperature can be induced by stress (so-cal...

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Section: Horiuchi Et Al Dmh Cardiovascular Response and 5-ht 1a Recepmentioning

confidence: 99%

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Activation of 5-Hydroxytryptamine 1A Receptors Suppresses the Cardiovascular Response Evoked From the Dorsomedial Hypothalamic Nucleus

2005

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“…The central role of EP3-receptors in PO/AH neurons in the fever response was demonstrated also by local knockdown of its expression [18]. The role of the DMH in the control of BAT thermogenesis was proven also by direct chemical or electrical stimulation [19]. These studies clearly revealed a tonic GABAergic inhibition of the DMH and rRPA by the PO/AH as crucial for basal thermoregulation and hyperthermic responses.…”

Section: Thermoregulatory Neuronal Network Comprising Po/ah Thermosementioning

confidence: 91%

Histaminergic Modulation of Body Temperature and Energy Expenditure

Tabarean¹

2013

Hyperthermia

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“…When excited or disinhibited, neurons in the DMH evoke tachycardia, hypertension, hyperthermia and increased locomotion in rats (Cao et al, 2004;DiMicco et al, 2006;Zaretskaia et al, 2002) --effects strikingly similar to those produced by systemic doses of MDMA. Conversely, microinjecting muscimol, a GABA A agonist and neuronal inhibitor, into the DMH suppresses tachycardia and hyperthermia elicited by either restraint stress or preoptic microinjections of prostaglandin E 2 (DiMicco et al, 1996;Zaretskaia et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Microinjection of muscimol into the dorsomedial hypothalamus suppresses MDMA-evoked sympathetic and behavioral responses

et al. 2008

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When given systemically to rats and humans, the drug of abuse 3-4 methylenedioxymethamphetamine (ecstasy, MDMA) elicits hyperthermia, hyperactivity, tachycardia, and hypertension. Chemically stimulating the dorsomedial hypothalamus (DMH), a brain region known to be involved in thermoregulation and in stress responses, causes similar effects. We therefore tested the hypothesis that neuronal activity in the DMH plays a role in MDMA-evoked sympathetic and behavioral responses by microinjecting artificial CSF or muscimol, a neuronal inhibitor, into the DMH prior to intravenous infusion of saline or MDMA in conscious rats. Core temperature, heart rate, mean arterial pressure and locomotor activity were recorded by telemetry every minute for 120 minutes. In rats previously microinjected with CSF, MDMA elicited significant increases from baseline in core temperature (+1.3 ± 0.3°C), locomotion (+50 ± 6 counts/min), heart rate (+142 ± 16 beats/min), and mean arterial pressure (+26 ±3 mmHg). Microinjecting muscimol into the DMH prior to MDMA prevented increases in core temperature and locomotion and attenuated increases in heart rate and mean arterial pressure. These results indicate that neuronal activity in the DMH is necessary for the sympathetic and behavioral responses evoked by MDMA. IntroductionThe popular drug of abuse 3,4-methylenedioxymethamphetamine (ecstasy or MDMA) is associated with numerous medical complications (Gowing et al., 2002). In both humans and laboratory animals, MDMA evokes complex physiologic and behavioral responses including, but not limited to, increases in locomotion (Spanos and Yamamoto, 1989), increases in heart rate and blood pressure (Dumont and Verkes, 2006;Rusyniak et al., 2007), and hyperthermia Corresponding Author: Daniel E Rusyniak, MD, Regenstrief Health Center, Suite R2200, 1050 Wishard Boulevard, Indianapolis, Indiana 46202-2859, Phone: (317) 287-3001, Fax (317) 656-4216, drusynia@iupui.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (Dumont and Verkes, 2006;Gowing et al., 2002). MDMA is thought to mediate these responses by facilitating monoaminergic neurotransmission. Indeed, numerous studies suggest that the responses evoked by MDMA involve receptors for serotonin, dopamine, and norepinephrine (Aguirre et al., 1998;Callaway et al., 1992;Green et al., 2004;Herin et al., 2005;Rusyniak et al., 2007; Sprague et al., 2004).Despite our current understanding of its pharmacology, the central sites and mechanisms by which MDMA evokes its responses are unknown. In part, this is due to complex interactions between neurotransmitters...

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Role of the dorsomedial hypothalamus in thermogenesis and tachycardia caused by microinjection of prostaglandin E2 into the preoptic area in anesthetized rats

Cited by 79 publications

References 17 publications

Activation of 5-Hydroxytryptamine 1A Receptors Suppresses the Cardiovascular Response Evoked From the Dorsomedial Hypothalamic Nucleus

Activation of 5-Hydroxytryptamine 1A Receptors Suppresses the Cardiovascular Response Evoked From the Dorsomedial Hypothalamic Nucleus

Histaminergic Modulation of Body Temperature and Energy Expenditure

Microinjection of muscimol into the dorsomedial hypothalamus suppresses MDMA-evoked sympathetic and behavioral responses

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