The dorsomedial hypothalamus and the response to stress

DiMicco, Joseph A.; Samuels, Brian C; Zaretskaia, Maria V.; Zaretsky, Dmitry V.

doi:10.1016/s0091-3057(01)00689-x

Cited by 271 publications

(218 citation statements)

References 86 publications

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“…The hypothalamus has long been implicated in generating a coordinated emotional arousal (see review (DiMicco et al, 2002)). More specifically, blockade of inhibitory GABA neurotransmission in the DMH/PeF elicits increases in HR and RR, BP, plasma catecholamine, adrenocorticotrophic hormone, and corticosterone concentrations, intestinal and colonic motility, and a pattern of peripheral blood flow that is similar to the pattern of peripheral blood flow during the defense reaction (see review (DiMicco et al, 2002)).…”

Section: Discussion Dmh/pef As One Putative Site Coordinating Panic-lmentioning

confidence: 99%

“…More specifically, blockade of inhibitory GABA neurotransmission in the DMH/PeF elicits increases in HR and RR, BP, plasma catecholamine, adrenocorticotrophic hormone, and corticosterone concentrations, intestinal and colonic motility, and a pattern of peripheral blood flow that is similar to the pattern of peripheral blood flow during the defense reaction (see review (DiMicco et al, 2002)). This pattern of autonomic responses is similar to that seen during panic attacks in humans (Liebowitz et al, 1986).…”

Section: Discussion Dmh/pef As One Putative Site Coordinating Panic-lmentioning

confidence: 99%

“…Removal of local tonic g-amino butyric acid (GABA)-mediated inhibition in the dorsomedial hypothalamic/ perifornical region (DMH/PeF) in rats results in rapid mobilization of a response characterized by behavioral, autonomic, respiratory, and endocrine components of panic-like responses (see review (DiMicco et al, 2002)). In light of this, Shekhar and colleagues developed an animal model of panic disorder where chronically inhibiting GABA synthesis in the DMH/PeF of rats leads to heightened anxiety and panic-like responses following exposure to i.v.…”

Section: Introductionmentioning

confidence: 99%

“…Since evidence from previous studies suggested that disinhibiting the DMH elicits cardioexcitatory responses by mobilizing sympathetic outflow (see review (DiMicco et al, 2002)) and resetting the sensitivity of the baroreflex, which is parasympathetically mediated (see review McDowall et al, 2006), we hypothesized that disinhibition of the DMH/PeF alters lactate-induced behavioral, respiratory, and cardiovascular responses through efferent targets involved in central sympathetic and parasympathetic autonomic control (Dampney, 1994;Thompson and Swanson, 1998;Fontes et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Neural Pathways Underlying Lactate-Induced Panic

Johnson

Truitt

Fitz

et al. 2007

Neuropsychopharmacol

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Panic disorder is a severe anxiety disorder characterized by susceptibility to induction of panic attacks by subthreshold interoceptive stimuli such as 0.5 M sodium lactate infusions. Although studied for four decades, the mechanism of lactate sensitivity in panic disorder has not been understood. The dorsomedial hypothalamus/perifornical region (DMH/PeF) coordinates rapid mobilization of behavioral, autonomic, respiratory and endocrine responses to stress, and rats with disrupted GABA inhibition in the DMH/PeF exhibit panic-like responses to lactate, similar to panic disorder patients. Utilizing a variety of anatomical and pharmacological methods, we provide evidence that lactate, via osmosensitive periventricular pathways, activates neurons in the compromised DMH/PeF, which relays this signal to forebrain limbic structures such as the bed nucleus of the stria terminalis to mediate anxiety responses, and specific brainstem sympathetic and parasympathetic pathways to mediate the respiratory and cardiovascular components of the panic-like response. Acutely restoring local GABAergic tone in the DMH/PeF blocked lactate-induced panic-like responses. Autonomic panic-like responses appear to be a result of DMH/PeF-mediated mobilization of sympathetic responses (verified with atenolol) and resetting of the parasympathetically mediated baroreflex. Based on our findings, DMH/PeF efferent targets such as the C1 adrenergic neurons, paraventricular hypothalamus, and the central amygdala are implicated in sympathetic mobilization; the nucleus of the solitary tract is implicated in baroreflex resetting; and the parabrachial nucleus is implicated in respiratory responses. These results elucidate neural circuits underlying lactate-induced panic-like responses and the involvement of both sympathetic and parasympathetic systems.

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Section: Discussion Dmh/pef As One Putative Site Coordinating Panic-lmentioning

confidence: 99%

Section: Discussion Dmh/pef As One Putative Site Coordinating Panic-lmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Neural Pathways Underlying Lactate-Induced Panic

Johnson

Truitt

Fitz

et al. 2007

Neuropsychopharmacol

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“…The dorsomedial hypothalamus (DMH) is one such site that coordinates neuroendocrine, autonomic, and behavioral responses for a variety of homeostatic mechanisms (Bernardis and Bellinger, 1998;DiMicco et al, 2002;Chou et al, 2003). Blocking GABA A neurotransmission in the DMH of rats elicits panic-like responses such as increases in heart rate (HR), respiratory rate (RR), mean arterial blood pressure (MAP), and experimental anxiety (DiMicco et al, 1986;DiMicco and Abshire, 1987;Shekhar, 1993).…”

Section: Introductionmentioning

confidence: 99%

Panic-Prone State Induced in Rats with GABA Dysfunction in the Dorsomedial Hypothalamus Is Mediated by NMDA Receptors

Johnson

Shekhar

2006

J. Neurosci.

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Critical role of B3 serotonergic cells in baroreflex inhibition during the defense reaction triggered by dorsal periaqueductal gray stimulation

Bernard¹,

Netzer²,

Gau³

et al. 2007

J of Comparative Neurology

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The present study was designed to identify the serotonergic pathway causing baroreflex inhibition associated with the defense reaction in rats. Under conditions that produce physiological responses typical of the defense reaction, electrical stimulation of the dorsal periaqueductal gray (dPAG) was found to double c-Fos immunoreactive serotonergic neurons within the mid-rostrocaudal extent of the B3 group (which comprises the raphe magnus and the lateral paragigantocellular reticular nuclei) in anesthetized rats. Local blockade of neuronal activity by microinjection of muscimol (a GABA(A) receptor agonist) directly into the B3 region prevented the inhibitory effect of dPAG activation on the cardiac baroreflex. Conversely, neuron activation by local application of D,L-homocysteic acid into B3 region caused baroreflex inhibition that was suppressed by microinjection of granisetron (a 5-HT(3) antagonist) into the nucleus tractus solitarius. These results show that activation of serotonergic cells in the mid-portion of B3 group is critical to trigger baroreflex inhibition occurring during the defense reaction evoked by dPAG stimulation.

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The dorsomedial hypothalamus and the response to stress

Cited by 271 publications

References 86 publications

Neural Pathways Underlying Lactate-Induced Panic

Neural Pathways Underlying Lactate-Induced Panic

Panic-Prone State Induced in Rats with GABA Dysfunction in the Dorsomedial Hypothalamus Is Mediated by NMDA Receptors

Critical role of B3 serotonergic cells in baroreflex inhibition during the defense reaction triggered by dorsal periaqueductal gray stimulation

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