Biomedical subjects

R Ursin

Publications and source records attributed to R Ursin.

At least 37 records · Page 2Linked to original sources

PubMed1994

Diurnal differences in L-tryptophan sleep and temperature effects in the rat.

Sleep/waking and EEG power spectra were investigated for 6 h periods in rats following administration of the essential amino acid L-tryptophan (40 mg/kg), the selective serotonin uptake inhibitor zimeldine (20 mg/kg), and following a combination of L-tryptophan and zimeldine. In contrast to earlier studies, L-tryptophan decreased waking and increased total slow wave sleep when administered late in the light phase (8 1/2 h after light onset). No sleep effects were seen after early light phase injections (2 h after lights on). In agreement with earlier studies, zimeldine initially increased wakefulness, followed by an increase in slow wave sleep-2. REM sleep was abolished after zimeldine treatment. Zimeldine increased EEG delta activity and decreased EEG activity above 7 Hz. L-Tryptophan potentiated the zimeldine induced increase in waking only when given early in the light phase. In a separate experiment, body temperature was monitored after L-tryptophan injections in both early and late light phase. A thermogenic effect of L-tryptophan was seen in the early light phase, while the opposite was seen in the late light phase. The data indicate diurnal differences in sleep/waking and temperature effects of a physiological dose of L-tryptophan.

Animals↗

PubMed1994

The reliability and functional validity of visual and semiautomatic sleep/wake scoring in the Møll-Wistar rat.

The present paper has three major objectives: first, to document the reliability of a published criteria set for sleep/wake scoring in the rat; second, to develop a computer algorithm implementation of the criteria set; and third, to document the reliability and functional validity of the computer algorithm for sleep/wake scoring. The reliability of the visual criteria was assessed by letting two raters separately score 8 hours of polygraph records from the light period from five rats (14,040 10-second scoring epochs). Scored stages were waking, slow-wave sleep-1, slow-wave sleep-2, transition type sleep and rapid eye movement (REM) sleep. The visual criteria had good interrater reliability [Cohen's kappa (kappa) = 0.68], with 92.6% agreement on the waking/nonrapid eye movement (NREM) sleep/REM sleep distinction (kappa = 0.89). This indicated that the criteria allow separate raters to independently classify sleep/wake stages with very good agreement. An independent group of 10 rats was used for development of an algorithm for semiautomatic computer scoring. A close implementation of the visual criteria was chosen. The algorithm was based on power spectral densities from two electroencephalogram (EEG) leads and on electromyogram (EMG) activity. Five 2-second fast Fourier transform (FFT) epochs from each EEG/EMG lead per 10-second sleep/wake scoring epoch were used to take the spatial and temporal context into account. The same group of five rats used in visual scoring was used to appraise reliability of computerized scoring. The computer score was compared with the visual score for each rater. There was a lower agreement (kappa = 0.57 and 0.62 for the two raters) than in interrater visual scoring [percent agreement 87.7 and 89.1% (kappa = 0.82 and 0.84) in the waking/NREM sleep/REM sleep distinction]. Subsequently, the computer scores of the raters were compared. The interrater reliability was better than the interrater reliability for visual scoring (kappa = 0.75), with 92.4% agreement for the waking/NREM sleep/REM sleep distinction (kappa = 0.89). The computer scoring algorithm was applied to data from a third independent group of rats (n = 6) from an acoustical stimulus arousal threshold experiment, to assess the functional validity of the scoring directly with respect to arousal threshold. The computer algorithm scoring performed as well as the original visual sleep/wake stage scoring. This indicated that the lower intrarater reliability did not have a significant negative influence on the functional validity of the sleep/wake score.

Algorithms↗

PubMed1994

Effects of the selective 5-HT1B agonist, CGS 12066B, on sleep/waking stages and EEG power spectrum in rats.

Sleep/waking stages and EEG power spectra were studied in rats for 8 h following intraperitoneal administration of CGS 12066B, a selective 5-HT1B agonist. Waking was increased and rapid eye movement (REM) sleep decreased in a dose-dependent manner. Total slow-wave sleep (TSWS) was reduced, but only in the first 2 h period. The latencies to REM sleep and stable sleep were increased dose-dependently. The drug also induced profound behavioural changes that may account for some of the sleep/waking changes. EEG power densities in waking and TSWS were reduced dose-dependently from 7 to 20 Hz after CGS 12066B, suggesting a tendency towards general deactivation. The increase in waking together with a general deactivation suggest complex effects of CGS 12066B on the sleep/waking axis.

Journal Article↗

PubMed1993

The 5-HT2 antagonist ritanserin decreases sleep in cats.

Sleep and wakefulness were recorded in cats after oral administration of the 5-HT2 antagonist ritanserin at doses of 0.5 and 1.0 mg/kg (n = 6), and after 2.5 mg/kg (n = 3). A subgroup (n = 4) of the animals also received the selective 5-HT uptake inhibitor zimeldine and a combination of ritanserin and zimeldine. The drugs were administered shortly after light onset, and sleep was recorded for 15 hours. Waking was increased and slow wave sleep (SWS), particularly deep slow wave sleep (SWS-2), was decreased throughout the recording time after ritanserin administration. Rapid eye movement (REM) sleep latency was increased, and the amount of REM sleep was reduced. In the combination study, ritanserin reduced the delayed SWS increase following the serotonin uptake inhibitor. The findings of increased waking and decreased SWS-2 after ritanserin in cats contrasts with findings from humans and rats where slow wave sleep is increased following ritanserin administration.

Animals↗

PubMed1993

Sleep stages and EEG power spectrum in relation to acoustical stimulus arousal threshold in the rat.

This study was designed to functionally validate earlier described criteria for visual sleep scoring with respect to acoustical stimulus threshold for arousal. A further objective was to explore the relation between electroencephalographic (EEG) power spectrum and acoustical stimulus threshold for arousal. After habituation to an acoustical stimulus (a 1,000-Hz sine tone, increasing 1.5 dB per second for 45 seconds), values for latency to arousal after acoustical stimulus onset were analyzed. Arousal was determined based on EEG and electromyographic (EMG) criteria. There was a significant effect of sleep stage, with slow wave sleep 2 (SWS-2) having higher arousal threshold than slow wave sleep 1 (SWS-1), rapid eye movement (REM) sleep and transition type sleep. This indicates that the subdivision of nonrapid eye movement (NREM) sleep in the rat into SWS-1 and SWS-2 had functional validity in this paradigm. Time of day also had a significant effect, with lower arousal threshold in the last 2 hours (ninth and tenth hour of the light period) of the 8-hour registration period. Furthermore, there was a significant effect of EEG delta power density. Epochs with high delta power had increased arousal threshold relative to epochs with low arousal threshold. The results were consistent with the notion that delta activity is an indicator of depth within NREM sleep.

Acoustic Stimulation↗

PubMed1992

The 5-HT1A antagonist (-)-alprenolol fails to modify sleep or zimeldine-induced sleep-waking effects in rats.

Sleep and waking in rats were studied for 8 h following administration of a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor (zimeldine), a putative 5-HT1A antagonist (L(-)-alprenolol hydrogene tartrate monohydrate [(-)-alprenolol]) and a combination of (-)-alprenolol and zimeldine. Consistent with earlier findings, zimeldine gave a biphasic effect on sleep and waking. Waking was increased during the first 3 h, followed by a small decrease. Deep slow-wave sleep (SWS-2) showed the opposite trend. An initial decrease in SWS-2 was followed by an increase after around 3 h. Rapid eye movement sleep was markedly suppressed and latencies to sleep increased after zimeldine. (-)-Alprenolol had no effects on the different sleep and waking stages or latencies to sleep. The 5-HT1A antagonist also failed to modify the effects of zimeldine administration. The behavioral syndrome induced by a selective 5-HT1A agonist [8-hydroxy-2-(di-n-propyl-amino)-tetralin (8-OH-DPAT)] was clearly antagonized by administration of (-)-alprenolol, indicating that (-)-alprenolol was an efficient 5-HT1A blocker. The data indicate that the sleep-waking effects of zimeldine cannot easily be explained by stimulation of 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1992

Studies on sleep/wake effects of serotonin reuptake inhibitors and receptor subtype involvement.

Studies with the serotonin uptake inhibitors zimeldine and alaproclate show biphasic effects on the sleep/wake axis in rats and cats. Zimeldine induced an initial waking response succeeded by a small SWS-2 increase in rats. The waking increase was not blocked by the 5-HT2 antagonist ritanserin nor by the putative 5-HT1A antagonist (-)-alprenolol. In cats, zimeldine induced initial behavioural changes which were succeeded by a large SWS-2 increase. Alaproclate gave similar initial responses as zimeldine in both species, and was succeeded by a moderate sleep increase in cats but not in rats. The complex sleep/wake effects following the serotonin uptake inhibitors may result from simultaneous induction of incompatible serotonergic effects.

Journal Article↗

PubMed1991

Behavioral, sleep-waking and EEG power spectral effects following the two specific 5-HT uptake inhibitors zimeldine and alaproclate in cats.

Sleep, waking and EEG power spectra were studied in cats for 15 h following peroral administration of placebo or 10 mg/kg and 20 mg/kg of the 5-HT reuptake inhibitors zimeldine and alaproclate. Behavior was also observed during the initial period following drug administration. Both drugs had effects on motor behavior and initiated hallucinatory like behavior. Zimeldine increased latency to stable sleep and to SWS-2. Alaproclate increased latency to SWS-1. Both drugs increased SWS (NREM sleep) and particularly SWS-2. REM sleep latency was increased and REM sleep was reduced following both drugs. EEG slow wave activity was increased following zimeldine. It is concluded that the 5-HT stimulation caused by the drugs yields complex effects on the sleep-waking axis, both sleep incompatible and sleep promoting effects.

Alanine↗

PubMed1990

Effects of zimeldine, a selective 5-HT reuptake inhibitor, combined with ritanserin, a selective 5-HT2 antagonist, on waking and sleep stages in rats.

Sleep and waking in rats were studied 8 h following administration of a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor (zimeldine), a selective 5-HT2 antagonist (ritanserin) and a combination of ritanserin and zimeldine. Consistent with earlier findings, zimeldine gave a biphasic effect on sleep and waking. Waking was increased the first 3 h, followed by an increase in deep slow wave sleep (SWS-2), maximal in hours 4 and 5. Ritanserin gave an increase in SWS-2 that was spread out over the recording period. Ritanserin + zimeldine also gave a biphasic effect as zimeldine did, and the initial increase in waking and the following increase in SWS-2 tended to be stronger. Thus, ritanserin did not block the initial waking effect seen after zimeldine administration, indicating that this waking effect was not due to 5-HT2 stimulation. The increase in SWS-2 seemed to reflect an addition of the increases following the zimeldine and ritanserin alone conditions. This suggests that the increase in SWS-2 seen after 5-HT reuptake inhibition and 5-HT2 blockade are independent phenomena. Zimeldine alone, ritanserin alone and the combination all gave a clear reduction of rapid eye movement sleep.

Animals↗

PubMed1989

Increased waking as well as increased synchronization following administration of selective 5-HT uptake inhibitors to rats.

Sleep and waking stages and EEG power spectra were investigated in rats following saline injections and injection of 10 and 20 mg/kg zimeldine or 10 and 20 mg/kg alaproclate, both selective 5-HT reuptake inhibitors. Following zimeldine there was a biphasic effect on sleep and waking, waking being increased during the first 2 1/2 h of recording, while slow wave sleep (SWS), in particular highly synchronized SWS-2 with high slow wave activity, was increased during the second 2 1/2 h recording period. Analysis of EEG power spectra indicated that the amount of synchronized slow wave activity was also increased within the sleep that occurred during the waking-dominated initial 2 1/2 h period. These data suggest simultaneous appearance of increased waking and increased synchronization following general serotonergic stimulation. They are interpreted as due to effects on different regions of the serotonergic system or on different serotonergic receptors. Consistent with earlier findings, zimeldine also suppressed rapid eye movement (REM) sleep. Following alaproclate, a clear waking effect was present, but only a weak synchronizing effect was seen. This is consistent with data on regional differences in uptake inhibition for zimeldine and alaproclate. Alaproclate also reduced REM sleep. Zimeldine or alaproclate was also administered to rats that had reduced sleep following pretreatment with a moderate dose of parachlorophenylalanine (PCPA). None of the drugs increased waking any further, but the PCPA-pretreated animals that received zimeldine had increased SWS-2, indicating that the SWS-2 increase following zimeldine alone was not a rebound effect.

Alanine↗

PubMed1989

EEG power spectra in rats during compression and during pentobarbital infusion at pressure.

The EEG of rats was studied with power spectrum analysis under compression to 71 ATA with He-O2 and during constant rate infusion of pentobarbital at 71 ATA and at surface. During compression the 1-4 Hz delta activity was increased, and 8-11 Hz alpha, 12-14 Hz spindle, and 16-10 Hz low beta activities were reduced compared to control animal recordings. During the course of pentobarbital infusion at 71 ATA, this picture changed: the delta activity was reduced while alpha and spindle activities (barbiturate spindles) increased, considerably more than in the rats studied at surface pressure. The findings may only in part be explained by pressure reversal of anesthesia.

Anesthesia↗

PubMed1987

Similar effect on REM sleep but differential effect on slow wave sleep of the two 5-HT uptake inhibitors zimeldine and alaproclate in cats and rats.

Sleep and waking in cats and rats were studied 6-10 hours following acute administration of zimeldine, alaproclate or saline. The effects on slow wave sleep of the two compounds markedly differed in the cats. Following zimeldine, sleep with a high amount of synchronized slow waves (SWS-2) was increased, and total sleep was unchanged. Following alaproclate, SWS-2 did not increase, and total sleep was reduced. In the rats, zimeldine increased SWS-2 during the first 4 hours after administration, while there was no change in SWS following alaproclate. Both zimeldine and alaproclate increased REM latency and reduced REM sleep in both species with somewhat more pronounced effects in cats than in rats. The results on SWS-2 following zimeldine are consistent with earlier results following serotonin depletion in both species. The differential effects on SWS-2 are discussed in terms of regional differences in uptake inhibition and other differences between the two uptake inhibitors. The results on REM sleep confirm earlier results involving serotonin uptake inhibitors and serotonin precursor loading and indicate that increased synaptic serotonin concentrations suppress REM sleep.

Alanine↗

PubMed1987

The effects of zimeldine and alaproclate combined with a small dose of 5-HTP on waking and sleep stages in cats.

Sleep and waking stages in cats were studied 8 h following administration of zimeldine and alaproclate, in combination with saline or 5-hydroxy-1-tryptophan (5-HTP). Both drugs in combination with saline reduced rapid eye movement sleep and ponto-geniculo-occipital wave activity, and the effects were potentiated with 5-HTP. After administration of zimeldine in combination with 5-HTP there was an increase in synchronized waking (W-2), followed by an increase in slow wave sleep (SWS), at first SWS-1 with spindles and then highly synchronized SWS-2. The changes were interpreted as reflecting a serotonergic deactivating effect expressed by an electroencephalographic synchronizing effect. This is consistent with earlier studies following serotonin depletion and serotonin precursor loading. After alaproclate in combination with 5-HTP there were changes in W-2 and SWS-1 suggestive of the same process but much less pronounced. The difference between the two serotonin uptake inhibitors is interpreted as being due to regional differences in their uptake inhibition.

5-Hydroxytryptophan↗

PubMed1987

Anesthetic effect and distribution of infused pentobarbital in the rat at 71 ATA.

The anesthetic dose requirement and distribution of 14C-labeled pentobarbital were studied in rats at 1 ATA air and at 71 ATA He-O2. Pentobarbital was infused intravenously at a rate of 5 mg X kg-1 X min-1. The depth of anesthesia was assessed by EEG using the burst suppression of 1-s duration (silent second) as the biological end point. The mean anesthetic dose was 45.6 and 68.0 mg X kg-1 at 1 and 71 ATA, respectively, representing a 49% increase at pressure (P less than 0.001). The corresponding concentrations in the brain were 81.6 and 92.3 micrograms X g-1 (not significant). The hepatic and renal pentobarbital concentrations increased by 44 and 41%, respectively, at pressure (P less than 0.001). Interindividual variations in required doses and infusion lengths made comparison between tissue pentobarbital values difficult to interpret. A second series of experiments was therefore undertaken using a subanesthetic dose of pentobarbital infused at the same constant rate for 7 min. No significant changes were found in the organ distribution of the drug at pressure. The results show that high pressure antagonizes the narcotic effect of pentobarbital and that the distribution of pentobarbital is not significantly altered in the rat at 71 ATA.

Anesthesia↗

PubMed1985

Platform sleep deprivation affects deep slow wave sleep in addition to REM sleep.

Rats were sleep deprived by the platform method to look for differential effects on light and deep slow wave sleep depending on platform size. Diameters of large and small platforms were 15 cm and 5.1 cm respectively. Sleep was recorded during a baseline light period (09.00-19.00 h), continuously during 48 h of sleep deprivation and during the first lights on recovery period (09.00-19.00 h). In both platform conditions REM sleep was virtually abolished during the first light period (hours 0-10 of sleep deprivation), while NREM sleep was reduced to approximately half of control values. During the second light period (hours 22-34 of sleep deprivation) REM sleep recovered somewhat in the large platform group. Light slow wave sleep (SWS-1) was comparable to baseline while deep slow wave sleep (SWS-2) was still significantly reduced. In the small platform group both SWS-2 and REM sleep was considerably reduced on day 2. Over the whole deprivation period there was an effect of platform size on SWS-1 (higher in the small platform group), and on SWS-2 and REM sleep (lower in the small platform group). During the 9 h light-time recovery sleep there was an REM sleep rebound in both groups. SWS-1 was reduced in both groups while SWS-2 was not significantly increased. The ratio SWS-2/SWS-1 was, however, significantly increased only in the small platform group recovery sleep. The results suggest that platform sleep deprivation deprives the animals of deep slow wave sleep in addition to REM sleep. This has implications for conclusions on REM sleep function based upon REM sleep deprivation.

Animals↗

PubMed1983

Increased sleep following intracerebroventricular injection of the delta sleep-inducing peptide in rats.

Synthetic delta sleep-inducing peptide (DSIP) was injected intracerebroventricularly into rats in a dose of 7 nmol/kg. A significant, 20% increase in total slow wave sleep (and total sleep) was found in the DSIP-injected rats, compared to a baseline recording following a sham injection procedure. Rats injected with the Ringer solution vehicle did not change their sleep compared to their baseline recording.

Animals↗

PubMed1983

The effect of sleep deprivation and recovery sleep on plasma corticosterone in the rat.

The effect of 24-h sleep deprivation by forced locomotion on plasma corticosterone was investigated in the rat. Corticosterone was slightly elevated after 21.5 h sleep deprivation, but did not differ from controls after a 2.5-h recovery period. An acute 20-min forced locomotion period caused a marked rise in plasma corticosterone. It is concluded that stress is not a major factor contributing to the massive effects of sleep deprivation on sleep parameters.

Animals↗

PubMed1983

L-tryptophan: effects on daytime sleep latency and the waking EEG.

The effects of L-tryptophan (4 g) on the waking EEG and daytime sleep were studied in a group of 20 normal adults. Subjects were assigned to a morning or afternoon group, and data were collected on two occasions, after L-tryptophan and after placebo, assigned in a counterbalanced order. L-Tryptophan significantly reduced sleep latency without altering nap sleep stages and elevated plasma total and free tryptophan levels. EEGs were digitized on-line and later analyzed for changes in 5 frequency bands: 16-40 c/sec (beta), 13.0-15.5 c/sec (sigma), 8.0-12.5 c/sec (alpha), 4.0-7.5 c/sec (theta) and 0.5-3.5 c/sec (delta). During waking EEGs, L-tryptophan significantly increased alpha time, theta time, and theta intensity and significantly decreased alpha frequency. No wave bands were altered during sleep. L-Tryptophan is an effective daytime hypnotic which can facilitate sleep onset at clock times which do not coincide with biological sleep times. The hypnotic effects may be mediated by lowering arousal level during the awake state, thus setting the stage for more rapid sleep onset.

Adult↗