Thesis (Ph.D.)--Indiana University, 2010. / Title from screen (viewed on March 3, 2010). Department of Pharmacology and Toxicology, Indiana University-Purdue University Indianapolis (IUPUI). Advisor(s): Joseph A. DiMicco, Sherry F. Queener, Daniel E. Rusyniak, Michael R. Vasko. Includes vitae. Includes bibliographical references (leaves 126-147).

Thesis (Ph.D.)--Indiana University, 2009. / Title from screen (viewed on August 27, 2009). Department of Medical Neuroscience, Indiana University-Purdue University Indianapolis (IUPUI). Advisor(s): Joseph DiMicco. Includes vita. Non-Latin script record Includes bibliographical references (leaves 123-140).

Indiana University-Purdue University Indianapolis (IUPUI) / Recent studies in anesthetized rats suggest that autonomic effects relating to thermoregulation that are evoked from the preoptic area (POA) may be mediated through activation of neurons in the dorsomedial hypothalamus (DMH). Disinhibition of neurons in the DMH produces not only cardiovascular changes but also increases in plasma adrenocorticotropic hormone (ACTH) and locomotor activity mimicking those evoked by microinjection of muscimol, a GABAA receptor agonist and neuronal inhibitor, into the POA. Therefore, I tested the hypothesis that all of these effects evoked from the POA are mediated through neurons in the DMH by assessing the effect of bilateral microinjection of muscimol into the DMH on the changes evoked by microinjection of muscimol into the POA in conscious rats. In addition, I tested the hypothesis that neurons in the DMH mediate a specific response that is thought to signal through the POA, the activation of the HPA axis evoked by systemic administration of the inflammatory cytokine IL-1β. After injection of vehicle into the DMH, injection of muscimol into the POA elicited marked increases in heart rate, arterial pressure, body temperature, plasma ACTH and locomotor activity and also increased Fos expression in the hypothalamic paraventricular nucleus (PVN), a region known to control the release of ACTH from the adenohypophysis, and the raphe pallidus, a medullary region known to mediate POA-evoked sympathetic responses. Prior microinjection of muscimol into the DMH produced a modest depression of baseline heart rate, arterial pressure, and body temperature but completely abolished all changes evoked from the POA. Microinjection of muscimol just anterior to the DMH had no effect on POA-evoked autonomic and neuroendocrine changes. Inhibition of neuronal activity in the DMH only partially attenuated the increased activity of the HPA axis following systemic injections of IL-1β. Thus, neurons in the DMH mediate a diverse array of physiological and behavioral responses elicited from the POA, suggesting that the POA represents an important source of inhibitory tone to key neurons in the DMH. However, it is clear that the inflammatory cytokine IL-1β must employ other pathways that are DMH-, and possibly POA-, independent to activate the HPA axis.

Indiana University-Purdue University Indianapolis (IUPUI) / Brain responds to an array of diverse challenges that are defined as either exteroceptive stress, involving cognitive processing of sensory information from the external environment and or interoceptive stress, detected through sensory neural or chemical cues from the internal environment. The physiological response to most stresses consists of autonomic responses that are essential for animal survival in the face of a threatening circumstance. However, it is known that exposition to continuous situations of stress is involved in the development of a series of diseases such as hypertension, myocardial infarction and panic syndrome. Several studies have shown that cells in a specific area of the brain, the dorsomedial hypothalamus (DMH), are involved in the response produced during emotional stress. However, the role of glutamatergic transmission in the DMH in the increase in body temperature induced by experimental stress has not been examined. Research findings thus far indicate that neurons in the DMH play a role in thermoregulation and that local glutamate receptors may be involved. The hypothesis of this thesis is that activity at ionotropic glutamate receptors in the DMH is necessary for the thermogenic response induced by experimental stress. In the present work, microinjections of kynurenate, an excitatory amino acid antagonist, NBQX (2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione), an AMPA/kainate receptor antagonist, DL-2-amino-5-phosphonovaleric acid (APV), an NMDA receptor antagonist, and a mixture of NBQX and APV, were delivered to the DMH before exposure to experimental stress. The stress paradigms used include models for exteroceptive stress and interoceptive stress. The results show that inhibition of both NMDA and non-NMDA receptors is necessary to abolish the thermogenic response produced by all stress paradigms tested. Furthermore, there appears to be a difference in the degree of attenuation of the thermogenic response produced by either inhibition of NMDA receptors or non-NMDA receptors. Together these results support a definite role for ionotropic glutamate receptors within DMH region in the thermogenic response to stress. These results also finally show that the DMH is involved in all the major physiological stress responses including increase in plasma ACTH, increase in heart rate, blood pressure and now temperature as well.