Browsing by Subject "body temperature"

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    Circadian variability of body temperature responses to Methamphetamine (Meth)
    (Office of the Vice Chancellor for Research, 2015-04-17) Behrouzvaziri, Abolhassan; Yoo, Yeonjoo; Morozova, Ekaterina; Zaretskaia, Maria; Zaretsky, Dmitry; Molkov, Yaroslav
    Vital parameters of living organisms exhibit circadian rhythmicity. Despite rats are nocturnal animals, most of drugs of abuse studies in rodents are performed during the day. Virtually no data on circadian variability of responses to amphetamines is currently available. However, the amplitude of circadian variations of body temperature is comparable to the magnitude of temperature responses to Meth. Accordingly, one can expect that the responses may be qualitatively different during the day and at night. Experiments were performed on male Sprague-Dawley rats implanted with telemetric probes reporting body temperature. Rats received i.p. injections of Meth (1 or 5 mg/kg) or saline at 10-11am or at 10-11pm. Each rat received only one injection of Meth to avoid the effects of repeated administration. The responses were recorded for at least 5 h. The baseline body temperature at night was 0.8ºC higher than during the day. The body temperature increased after injections of saline during both day and night but returned to its baseline within 1 h. This response was developing faster, and more pronounced at night. The temperature responses to Meth were different during the day and at night. In both cases the lower dose of Meth (1 mg/kg) induced monophasic hyperthermia. However, the maximal deviation of the temperature from baseline was appr. twice smaller at night than during the day. Injection of the higher dose of Meth (5 mg/kg) at day time caused a delayed hyperthermic response, preceded by a slight increase of the body temperature immediately after injection. In contrast, at night the same dose produced immediate hypothermia, which was not observed during the day. Recently, we created a model which showed that the complex dose-dependence of day-time temperature responses to Meth results from the delicate balance between inhibitory and excitatory drives which have different sensitivity to the drug. To interpret the night time data, we extended this mathematical model by assuming that the excitatory and/or inhibitory components and general metabolism are affected by the circadian input. Our model revealed that during the night the baseline activity of the excitatory node is greater than during the day. Besides, after injection of either dose of Meth the equilibrium body temperature appears significantly lower than the temperature observed before injection. The suppression of the response to the lower dose of Meth is, therefore, explained by a combination of two factors. First, the excitatory drive, which is predominantly responsible for monophasic hyperthermia after low doses of Meth, gets partially saturated. Second, the reduced general metabolism, which underlies the lower equilibrium temperature, leads to gradual cooling thus limiting the hyperthermia. Same mechanisms mediate the observed hypothermia during the night after the higher dose of Meth, as the inhibitory drive starts dominating the excitatory one. The reduction of the equilibrium temperature after Meth injection during the active time period represents a major perturbation of the thermoregulatory system status, and may reflect a Meth-triggered disturbance of circadian rhythmicity.
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    Meth math: modeling temperature responses to methamphetamine
    (American Physiological Society (APS), 2014-04-15) Molkov, Yaroslav I.; Zaretskaia, Maria V.; Zaretsky, Dmitry V.; Department of Emergency Medicine, IU School of Medicine
    Methamphetamine (Meth) can evoke extreme hyperthermia, which correlates with neurotoxicity and death in laboratory animals and humans. The objective of this study was to uncover the mechanisms of a complex dose dependence of temperature responses to Meth by mathematical modeling of the neuronal circuitry. On the basis of previous studies, we composed an artificial neural network with the core comprising three sequentially connected nodes: excitatory, medullary, and sympathetic preganglionic neuronal (SPN). Meth directly stimulated the excitatory node, an inhibitory drive targeted the medullary node, and, in high doses, an additional excitatory drive affected the SPN node. All model parameters (weights of connections, sensitivities, and time constants) were subject to fitting experimental time series of temperature responses to 1, 3, 5, and 10 mg/kg Meth. Modeling suggested that the temperature response to the lowest dose of Meth, which caused an immediate and short hyperthermia, involves neuronal excitation at a supramedullary level. The delay in response after the intermediate doses of Meth is a result of neuronal inhibition at the medullary level. Finally, the rapid and robust increase in body temperature induced by the highest dose of Meth involves activation of high-dose excitatory drive. The impairment in the inhibitory mechanism can provoke a life-threatening temperature rise and makes it a plausible cause of fatal hyperthermia in Meth users. We expect that studying putative neuronal sites of Meth action and the neuromediators involved in a detailed model of this system may lead to more effective strategies for prevention and treatment of hyperthermia induced by amphetamine-like stimulants.
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    Role of the Dorsomedial Hypothalamus in Responses Evoked from the Preoptic Area and by Systemic Administration of Interleukin-1β
    (2009-06-23T21:35:36Z) Hunt, Joseph L.; DiMicco, Joseph A.; Cummins, Theodore R.; Rusyniak, Daniel; Vasko, Michael R.
    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.