-
[show abstract]
[hide abstract]
ABSTRACT: Metyrapone is a glucocorticoid synthesis inhibitor largely used to study glucocorticoid involvement in stress and memory processes. Metyrapone also acts as a stressor and therefore might modify sleep/wake patterns. However, its effects on rat sleep are unknown. We equipped 8 rats for telemetric assessment of EEG and EMG. They received first a saline injection and 2days later a 150mg/kg metyrapone injection. Metyrapone provoked immediately a waking effect together with a 3-h decrease in slow-wave sleep (SWS) and a 5-h decrease in rapid eye movement sleep (REM sleep). Thereafter, the rats exhibited homeostatic compensation through SWS and REM sleep rebounds recovering totally the sleep debt. The finding that metyrapone modified sleep patterns is important to consider for stress and memory studies using metyrapone.
European journal of pharmacology 02/2011; 652(1-3):60-4. · 2.59 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Low spontaneous locomotor activity (SA) represents a thermoregulatory behaviour that aims at improving heat tolerance. However, high SA is observed during heat exposure. We hypothesized that high SA could be associated to brain dysfunction. Eighty male Sprague-Dawley rats were heat exposed for 90-min under a continuous assessment of SA and abdominal temperature (T(abd)) using telemetry. The time course analysis showed two SA peaks. The first one was related to exposure to novel environment, the second to heat. The maximal SA level reached in the second peak served to distribute the rats into three groups (LOW, MED and HIGH). In each SA pattern group, heat tolerance was estimated from T(abd) values. At the end of heat exposure, frontal cortex activation was assessed using c-fos, Hsp70 and IkappaBalpha mRNA expressions. The LOW rats exhibited the lowest T(abd), a slight increase in c-fos and Hsp70 mRNA expressions and a robust increase in IkappaBalpha mRNA expression. The HIGH rats exhibited the highest T(abd) and a robust increase in c-fos and Hsp70 mRNA expressions without any change in IkappaBalpha mRNA expression. The c-fos and Hsp70 mRNA expressions were positively correlated to the highest SA levels occurring 45 min before sacrifice, suggesting that high SA and frontal cortex activation are related. In conclusion, high SA is associated to decreased heat tolerance and frontal cortex activation. It may represent a marker of inadequate stress reaction.
Behavioural brain research 03/2010; 211(1):41-7. · 3.22 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Metyrapone, a cytochrome P(450) inhibitor used to inhibit corticosterone synthesis, triggers biological markers of stress and also reduces stress-induced anxiety-like behaviors. To address these controversial effects, 6 separate investigations were carried out. In a first set of investigations, abdominal temperature (T(abd)), spontaneous locomotor activity (A(S)) and electroencephalogram (EEG) were recorded in freely moving rats treated with either saline or 150 mg kg(-1) metyrapone. An increase in T(abd) and A(S) occurred in saline rats, while, metyrapone rats exhibited an immediate decrease, both variables returning to basal values 5h later. Concomitantly, the EEG spectral power increased in the gamma and beta 2 bands and decreased in the alpha frequency band, and the EMG spectral power increased. This finding suggests that metyrapone depressed stress-induced physiological response while arousing the animal. In a second step, restraint stress was applied 5h after injection. Metyrapone significantly blunted the stress-induced T(abd) and A(S) rise, without affecting the brain c-fos mRNA increase. Corticosterone (5 and 40 mg kg(-1)) injected concomitantly to metyrapone failed to reverse the observed metyrapone-induced effects in T(abd) and A(S). Finasteride (50 mg kg(-1)), which blocks neurosteroid production, was also unable to block these effects. In conclusion, metyrapone acutely reduced stress-induced physiological response in freely behaving rats independently from glucocorticoids and neurosteroids.
Psychoneuroendocrinology 03/2010; 35(9):1299-310. · 5.81 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Metyrapone is a glucocorticoid synthesis inhibitor known to induce a stress-like biological syndrome, but also to limit stress-related behaviours. Since stress is usually associated to an increased locomotion, the aim of the study was to determine whether metyrapone will increase, decrease or respect locomotion. Forty rats were placed in infrared actimeters to study spontaneous locomotion before and after injecting 150 mg kg(-1) of either metyrapone (n=20) or saline (n=20). Two hours after injection, half of each treatment group animals were tested in an open field to study test-evoked locomotion. Stress-induced analgesia was quantified using plantar test just before blood sampling. Immediately after injection, metyrapone decreased drastically horizontal and vertical locomotion. During the open field test, metyrapone-treated rats remained less active with slower movement execution than saline-treated rats. Metyrapone did not modify plantar test performances but blunted stress-induced corticosterone and ACTH increases. Mechanisms by which metyrapone induced these effects on locomotion are further discussed.
Neuroscience Letters 07/2009; 457(1):41-4. · 2.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: When exposed to heat, conscious naive rats may develop lethal heatstroke, depending on heat load, i.e., time spent at high body core temperature. The occurrence of heatstroke was hypothesized to result from a defective glucocorticoid secretion related to altered heat-stress responses. We thus investigated the potential involvement of glucocorticoids in heat tolerance and its consequences on physiological responses, heat shock protein 70 (Hsp70), and cytokine mRNA expressions. Two hours before heat exposure, the animals were injected either with metyrapone, an inhibitor of corticosterone synthesis, or with its vehicle. Heat exposure lasted for 15, 30, 45 or 60 min. Thereafter, the rats were distributed into three groups according to their heat load: null, moderate (without any lethal risk) and intense (with lethal risk). Physiological responses were evaluated with colonic temperature, plasma lactate and hematocrit. Brain responses were assessed in frontal cortex through Hsp70, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) mRNA expressions. The animals with a severe heat load exhibited a high hematocrit, increased plasma lactate level and enhanced brain IL-1beta and Hsp70 mRNA expressions. Independent of the heat load, Metyrapone rats showed the same thermophysiological responses and IL-1beta and Hsp70 mRNA expressions when compared with vehicle rats. However, the Metyrapone rats experiencing an intense heat load exhibited an increased TNF-alpha mRNA expression. In conclusion, these data (i) confirm that heat load is important in the calibration of the risk attached to heat exposure; and (ii) suggest that corticosterone synthesis inhibition may favor TNF-alpha mRNA expression without any effect on Hsp70 mRNA expression.
Brain Research 09/2007; 1164:63-71. · 2.73 Impact Factor
-
Revista cubana de medicina tropical 54(1):7-10.
