Letícia L. Lobo

Increased ACTH and corticosterone secretion induced by different methods of paradoxical sleep deprivation.

The methods used to induce paradoxical sleep (PS) deprivation are believed to be stressful. In the present study, two methods were compared in regard to their ability to activate the hypothalamic‐pituitary‐adrenal (HPA) axis. Animals were placed on multiple large (MLP) or small (MSP) platforms or on single large (SLP) or small (SSP) platforms and blood sampled at the end of a 4‐day period of PS deprivation (experiment 1) or on Days 1 (short‐term) and 4 (long‐term) of PS deprivation (experiment 2). ACTH and corticosterone (CORT) levels were determined by RIA. The results of experiment 1 showed that all experimental animals presented increased ACTH response, compared to controls. CORT levels, however, were only elevated in MSP animals, suggesting increased adrenal sensitivity. Experiment 2 showed that ACTH levels of MSP animals were higher than MLP and SSP animals, and that animals placed on the multiple platform tanks showed the highest ACTH levels on Day 4 of manipulation. CORT levels were elevated in the animals kept over small platforms, and these levels where higher on Day 1 than basal and further elevated on Day 4 of PS deprivation. These results indicate that the multiple platform technique induces a distinct activation of the HPA axis, and that PS deprivation may act as an additional stressor.

Dissociated paradoxical sleep deprivation effects on inhibitory avoidance and conditioned fear

Rats were submitted to paradoxical sleep deprivation (PSD) for 24, 72, or 96 h and were trained on a double aversively motivated task, encompassing a step-through inhibitory avoidance and a classical conditioning of fear to a brief tone serving as conditional stimulus. Retention test of the inhibitory avoidance was performed at the same apparatus of training (without tone presentation). Retention of conditioned fear was assessed in an open field apparatus, where the freezing reaction to the tone was measured. PSD for 24 and 72 h preceding the training session had no effect on either task. However, PSD during the 96 h preceding the training session impaired acquisition of inhibitory avoidance, but had no effect on classically conditioned fear. It is concluded that PSD had differential effects on the two tasks, both aversively motivated and trained at the same time and conditions.

Absence of oxidative stress following paradoxical sleep deprivation in rats

Paradoxical sleep deprivation was performed on rats using platform technique to investigate the oxidative process associated with it. Levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), total glutathione (GSH) and malondialdehyde production were measured in brain of rats under control conditions (C) and those on single large platforms (SLP), multiple large platforms (MLP), single small platforms (SSP) and multiple small platforms (MSP) groups. SOD, CAT and GPx brain activity and malondialdehyde production were not modified by any of the procedures. Brain GSH, however, was significantly reduced in both SSP and SLP groups. These results suggest that paradoxical sleep deprivation per se is not associated with oxidative damage. The observed alterations could be attributed to factors such as immobilization and social isolation present in the single platform techniques.

Effects of a prolonged administration of valepotriates in rats on the mothers and their offspring

Valeriana officinalis L. (Valerianaceae) is widely known to be associated with sedative properties. The effects of a valepotriates mixtures on mothers and progeny were evaluated in rats. A 30-day administration of valepotriates did not change the average length of estral cycle, nor the number of estrous phases during this period. Also, there were no changes on the fertility index. Fetotoxicity and external examination studies did not show differences, although internal examination revealed an increase in number of retarded ossification after the highest doses employed--12 and 24 mg/kg. No changes were detected in the development of the offspring after treatment during pregnancy. As for temperature, valepotriates caused a hypothermizant effect after administration by the intraperitoneal route but not after oral administration. Generally, the valepotriates employed induced some alterations after administration by the intraperitoneal route, but doses given orally were innocuous to pregnant rats and their offspring.

Effects of Stress on Drug-Induced Yawning: Constant Vs. Intermittent Stress

Effects of stress on drug-induced yawning: Constant vs. intermittent stress. PHYSIOL BEHAV 58(1) 181-184, 1995.--Experiment 1 tested whether chronic exposure to immobilization, foot shock or forced swimming would result in suppression of apomorphine-, pilocarpine-, and physostigmine-induced yawning. Immobilization caused suppression of yawning, whereas foot shock and swimming resulted in increased number of yawns. Since interstressor interval was long in the two latter stressors, animals could have recovered and the increase in yawning could be due to the last (acute) exposure to stress. In Experiment 2 we recorded the number of yawns induced by pilocarpine in animals exposed to 1 h of swimming or foot shock. No differences between control and acutely stressed animals were detected. These results suggest that yawning is differently altered by constant and intermittent stressors (i.e., diminished by constant and increased by intermittent stress).

Chounergic modulation of inhibitory avoidance impairment induced by paradoxical sleep deprivation

1. Male Wistar rats were submitted to paradoxical sleep deprivation for 96 hr by a modified multiple platform technique. 2. Training of step-through inhibitory avoidance was performed immediately after the last day of paradoxical sleep deprivation. Twenty-four hr after training the animals were submitted to the retention test. 3. In Experiment 1, pilocarpine (4 mg/kg, i.p.) or atropine (4 mg/kg, i.p.) were administered daily during the paradoxical sleep deprivation period. Pilocarpine, but not atropine, reversed the impairment induced by PS deprivation. 4. In Experiment 2, pilocarpine (4, 8 and 12 mg/kg, i.p.) was injected 1 hr before training in order to verify if the reversal of memory impairment was an effect secondary to residual enhanced blood levels of pilocarpine during training. Acute treatment with pilocarpine, in any dose, did not reverse the impairment produced by paradoxical sleep deprivation 5. Activation of the cholinergic system during the period of deprivation is able to prevent memory deficits induced by paradoxical sleep deprivation.

Melatonin treatment does not prevent decreases in brain glutathione levels induced by sleep deprivation

Recent findings from this laboratory revealed that sleep deprivation reduces total glutathione (GSH) levels in hypothalamus, suggesting an increased vulnerability to oxidative damage. Since melatonin has been shown to prevent oxidative damage in other experimental situations, the present study tested the effects of exogenous melatonin on sleep deprivation-induced GSH decreases. Rats were deprived of sleep for 96 h on small platforms, and melatonin (10 mg/kg body weight; i.p.) or vehicle was given twice a day. Hypothalamic GSH levels were significantly reduced in sleep-deprived groups, irrespective of melatonin treatment. Indeed, unexpectedly, melatonin treatment resulted in lower hypothalamic GSH levels in all groups, including cage controls. These results confirm that sleep deprivation reduces hypothalamic GSH and further indicate that melatonin treatment not only is ineffective in reversing this effect but may actually potentiate it.

Effects of REM Sleep Deprivation on ACTH-induced Yawning

Central administration of ACTH in rats induces yawning and stretching. In order to study the effects of REM sleep deprivation on ACTH-induced yawning, the peptide was injected immediately after the REM sleep deprivation period or 24 h later. REM sleep deprivation impaired ACTH-induced yawning, but after a 24-hour recovery period, rats displayed a number of yawns similar to those in control animals. Implications for an involvement of dopaminergic and mainly cholinergic systems are discussed.

Treatment with dexamethasone alters yawning behavior induced by cholinergic but not dopaminergic agonist.

Because stressful manipulations have been reported to modify drug-induced yawning, the present study investigated the effects of single and repeated treatment with a synthetic glucocorticoid, dexamethasone (DEXA) on apomorphine- and pilocarpine-induced yawning in male rats. Neither single nor repeated treatment with DEXA altered apomorphine-induced yawning. Single administration of DEXA, however, resulted in an increased number of yawns induced by pilocarpine. Conversely, repeated administration of DEXA led to a decreased number of yawns induced by pilocarpine. In conclusion, the present findings show that dopaminergic and cholinergic are distinctly altered by DEXA, in terms of yawning behavior when animals received DEXA.

Atropine increases pilocarpine-induced yawning behavior in paradoxical sleep deprived rats

Paradoxical sleep (PS) deprivation has been suggested to induce supersensitivity of postsynaptic dopamine (DA) receptors and subsensitivity of acetylcholine (ACh) receptors. Yawning behavior is reduced after PS deprivation and is believed to result from an interaction between ACh and DA systems. Concomitant treatment of PS deprived animals with DA agonists reverses PS deprivation effects on stereotypy and aggressiveness. To examine this possibility on yawning behavior, rats were treated, during the deprivation period, with atropine, methamphetamine, haloperidol or distilled water. Following PS deprivation, rats were injected with apomorphine or pilocarpine and number of yawns was recorded. Atropine increased yawning of PS deprived rats induced by pilocarpine, but not by apomorphine. Treatment with methamphetamine and haloperidol did not change PS deprivation effect on pilocarpine- and apomorphine-induced yawning. The data suggest that reversal of PS deprivation-induced yawning inhibition is mediated distinctly by both acetylcholine and dopamine systems.