Decrease In Rapid Eye Movement Sleep Research Articles

Deficiency of Growth Hormone-Releasing Hormone Signaling Is Associated with Sleep Alterations in the Dwarf Rat

The somatotropic axis, and particularly growth hormone-releasing hormone (GHRH), is implicated in the regulation of sleep-wake activity. To evaluate sleep in chronic somatotropic deficiency, sleep-wake activity was studied in dwarf (dw/dw) rats that are known to have a defective GHRH signaling mechanism in the pituitary and in normal Lewis rats, the parental strain of the dw/dw rats. In addition, expression of GHRH receptor (GHRH-R) mRNA in the hypothalamus/preoptic region and in the pituitary was also determined by means of reverse transcription-PCR, and GHRH content of the hypothalamus was measured. Hypothalamic/preoptic and pituitary GHRH-R mRNA levels were decreased in the dw/dw rats, indicating deficits in the central GHRHergic transmission. Hypothalamic GHRH content in dw/dw rats was also less than that found in Lewis rats. The dw/dw rats had less spontaneous nonrapid eye movement sleep (NREMS) (light and dark period) and rapid eye movement sleep (REMS) (light period) than did the control Lewis rats. After 4 hr of sleep deprivation, rebound increases in NREMS and REMS were normal in the dw/dw rat. As determined by fast Fourier analysis of the electroencephalogram (EEG), the sleep deprivation-induced enhancements in EEG slow-wave activity in the dw/dw rats were only one-half of the response in the Lewis rats. The results are compared with sleep findings previously obtained in GHRH-deficient transgenic mice. The alterations in NREMS are attributed to the defect in GHRH signaling, whereas the decreases in REMS might result from the growth hormone deficiency in the dw/dw rat.

The selective 5-HT 1A receptor antagonist p-MPPI antagonizes sleep–waking and behavioural effects of 8-OH-DPAT in rats

Systemic administration of the selective 5-HT 1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin HBr (8-OH-DPAT) increases waking and reduces slow wave sleep (SWS) and rapid eye movement (REM) sleep in the freely moving rat. The selective 5-HT 1A antagonist 4-(2′-methoxy-phenyl)-1-[2′-(n-2″-pyridinyl)- p-iodobenzamido]-ethyl-piperazine ( p-MPPI) induces a dose-related decrease in REM sleep. The present study examined p-MPPI's potential as an antagonist of the sleep and waking responses elicited by 8-OH-DPAT. Also, the experiments explored the ability of p-MPPI to block behavioural reactions of the 5-HT syndrome induced by 8-OH-DPAT, and whether p-MPPI induced any behavioural effects of its own. This study demonstrated that pre-treatment with p-MPPI (5 mg/kg intraperitoneal (i.p.)) 30 min before 8-OH-DPAT (0.375 mg/kg subcutaneously (s.c.)) reduced the effect of 8-OH-DPAT on waking and REM sleep. Also, p-MPPI (5 and 10 mg/kg i.p.) reduced the effect of 8-OH-DPAT on locomotion and partially or completely antagonized hindlimb abduction and flat body posture. No overt behavioural change was produced by p-MPPI alone. Thus, p-MPPI behaved as a true 5-HT 1A antagonist.

The Effects of Lipopolysaccharide (LPS) on the Fever Response in Rats at Different Ambient Temperatures

CONRAD, A., D. F. BULL, M. G. KING AND A. J. HUSBAND. The effects of lipopolysacchride (LPS) on fever response in rats at different ambient temperatures. PHYSIOL BEHAV 62(6) 1197–1201, 1997.—There is a complex interplay between the immune system, nervous system, and sleep. When an organism is challenged with lipopolysacchride (LPS), the immune system is stimulated, producing a fever response that is independent of ambient temperature, and an increase in slow-wave sleep (SWS). The study investigated sleep patterns of immune-challenged rats during the light phase cycle to determine the effects of various ambient temperatures. It was hypothesised that fever response would occur independently of ambient temperatures. Also, the febrile response would be monophasic, and there would be an increase in slow-wave sleep (SWS) and a decrease in rapid-eye-movement (REM) sleep. Thirty Wistar rats were randomly placed in 3 different ambient temperature groups, 22°C, 15°C, and 30°C. Within each of these conditions, the same subjects served as control and experimental groups. Four animals were placed in 4 subsections of 2 standard boxes that were placed in the ambient-temperature box. The electrodes were connected to the analog to digital computer board, where all the data was processed and stored on a hard drive. The animals were injected IP with saline and recorded for a period of 6 h to establish a baseline. On Day 2, the same animals were injected IP with LPS and recorded for 6 h to determine the febrile effects of LPS on the immune system; the same procedure was repeated in the other ambient temperatures. The results have shown that animals experienced a monophasic fever response in low and normal temperatures, but not in the high temperatures. Although there was no increase in SWS, there was a significant decrease in REM sleep in 3 groups.

Differential Effects of Total and Upper Airway Influenza Viral Infection on Sleep in Mice

Sleepiness is a common perception during most infectious diseases, including viral infections. Previously, we observed that a lethal strain of influenza virus (H1N1) causes a greater increase in non-rapid eye movement sleep (NREMS) than a nonlethal strain of influenza virus (H3N2), suggesting that the magnitude of sleep responses after viral inoculation depends on the severity of the infection. The aim of the present experiment was to further test this possibility. The effects of total airway infection versus upper airway infection on sleep were tested in two groups of mice using the same strain of virus (H1N1). After 2-3 days of baseline sleep recordings. Swiss-Webster mice were infected intranasally with H1N1 influenza virus. Sleep was determined again for an additional 3 days and 6 hours. Total airway infection significantly increased NREMS beginning about 24 hours after the viral inoculation and significantly suppressed rapid eye movement sleep (REMS) with a longer latency. Both the increase in NREMS and the decrease in REMS lasted until the end of the experiment. Total airway infection also significantly decreased the body weight of the mice. In contrast, upper airway infection did not induce clear changes in sleep and body weight.

Cardiorespiratory adaptation during sleep in infants and children.

The cardiorespiratory control system undergoes functional maturation after birth. Until this process is completed, the cardiorespiratory system is unstable, placing infants at risk for cardiorespiratory disturbances, especially during sleep. The profound influence of states of alertness on respiratory and cardiac control has been the focus of intense scrutiny during the last decade. The effects of rapid-eye movement (REM) sleep on various mechanisms involved in cardiorespiratory control are of particular significance during the postnatal period since newborns spend much of their time in this sleep state. In fullterm newborns, REM sleep occupies more than 50% of total sleep time, and this percentage is even greater in preterm newborns. From term to six months of age, the proportion of REM sleep decreases. Since respiratory and cardiac disturbances are known to occur selectively during REM sleep, the predominance of REM sleep may be a risk factor for abnormal sleep-related events during early infancy. Awareness of these developmental changes in sleep patterns is important for clinicians dealing with problems such as apparent life-threatening events (ALTE), sudden infant death syndrome (SIDS), and/or cardiorespiratory responses to respiratory disorders. Our current understanding of respiratory and cardiac control rests mainly on studies conducted during the first months of life. There is a paucity of data on late infancy and early childhood. The present paper will review available data on how sleep affects 1) ventilatory mechanics, in particular of the upper airways and the chest wall; ventilation and apnea; gas exchange; chemoreceptor function; and arousal responses; 2) changes in heart rate and heart rate variability, and the occurrence and mechanisms of bradycardia.

The influence of ipsapirone, a 5-HT1A agonist, on sleep patterns of healthy subjects

Ipsapirone is a new pyrimidinylpiperazine ligand specific for 5-HT1A receptors, with potential therapeutic use in affective disorders. Because 5-HT is involved in the regulation of sleep, we investigated the effect of ipsapirone hydrochloride on sleep patterns in 18 normal, healthy subjects of both sexes. Compared to placebo, ipsapirone 5 mg administered by mouth three times daily for 14 days decreased rapid eye movement (REM) sleep duration and, by the tenth day of treatment, began to reduce slow wave sleep (SWS) duration. The decrease in REM sleep occurred in the first 3 h of sleep. The latency to REM sleep was increased from the first night following ipsapirone administration, remained increased throughout the 14 days of administration, and fell to equal latency on placebo immediately administration ended. Subjective assessments of sleep revealed no differences between ipsapirone and placebo. Our experiments confirm a role of 5-HT1A receptors in sleep. The effects of ipsapirone on the sleep patterns of patients with affective disorders still need to be determined.

Effect of burn wound bacterial colonization on sleep and respiratory pattern

This study examined the effect of bacterial colonization of a burn wound on the sleep pattern and respiration during sleep. Sleep patterns of adult rats were monitored for one week before and two weeks after a 30 percent total body surface, full skin thickness burn with and without seeding the fresh wound with nonvirulent Pseudomonas aeruginosa. Unseeded rats were euthermic and exhibited a normal sleep pattern during the first-week post burn; however, rapid eye movement (REM) sleep percent was significantly decreased by the second week due to a reduction in the frequency rather than duration of REM periods. Rats with seeded wounds were febrile and had a significantly lower REM sleep percent throughout the two-weeks post burn due to a reduction in frequency but not duration of REM periods. The increase in respiratory rate from the non-REM to REM sleep state observed before injury was abolished in the seeded group post burn. There was an immediate but transient 24 h drop in REM sleep following thermal injury. Bacterial colonization of the burn wound by either immediate, artificial seeding or by delayed, spontaneous means significantly decreased REM sleep with and without fever, respectively. These results indicate that noninvasive bacterial colonization of a burn wound was capable of decreasing REM sleep without causing fever and that REM sleep reduction was a more sensitive indicator of the extent of burn wound bacterial colonization than was colonic temperature.

Gluco- and antimineralocorticoid effects on human sleep: a role of central corticosteroid receptors

Cortisol modulates brain functions in humans. This principal endogenous glucocorticoid in humans decreases rapid-eye-movement (REM) sleep and increases slow-wave sleep (SWS). Because cortisol exerts its effect on brain functions via mineralocorticoid receptors (MR) and glucocorticoid receptors (GR), we were interested in which type of corticosteroid receptor mediates these steroid effects on sleep. Healthy men were tested in two double-blind experiments. In experiment I (n = 8), the subject's sleep was tested during four nights: 1) after pretreatment with dexamethasone (Dex, 4 mg/day) for 4 or 6 days and after additional infusion of placebo or cortisol (10 mg/h) during the experimental night, 2) after pretreatment with placebo for 4 or 6 days and after infusion of placebo or cortisol (10 mg/h) during the experimental night. In experiment II, subjects (n = 10) slept after intravenous administration of potassium canrenoate (200 mg, at 0800 and 1700 h before experimental nights) or placebo. Cortisol infusion moderately increased the percentage of SWS (P less than 0.05) and markedly decreased REM sleep (P less than 0.01); influence of cortisol on SWS did not depend on pretreatment with Dex. Dex reduced both SWS and REM sleep (P less than 0.05). Canrenoate markedly diminished SWS (P less than 0.01) but left REM sleep unaffected. The results suggest that corticosteroid-induced changes in SWS are mediated via MR-like central receptors in humans, whereas changes in REM sleep involve GR.

Influences of Corticotropin-Releasing Hormone, Adrenocorticotropin, and Cortisol on Sleep in Normal Man*

We studied the effects of the hormones of the hypothalamus-pituitary-adrenocortical axis on sleep processes in normal men. In one experiment, 10 men received placebo, cortisol (6 mg/h), and ACTH (0.55 U/h) as continuous iv infusions from 2200-0700 h on 3 separate nights. In another experiment, placebo and CRH (30 micrograms/h) were administered to another 10 men in the same manner. The mean plasma cortisol levels were comparable during the cortisol and ACTH infusions (552 vs. 668 nmol/L). During both infusions, the time spent in rapid eye movement (REM) sleep was significantly (P less than 0.01) reduced compared to that during the placebo infusion, and the cortisol infusion significantly (P less than 0.05) enhanced the time spent in slow wave sleep (SWS). The CRH dose used only moderately increased plasma ACTH and cortisol levels; the changes in SWS and REM sleep during CRH infusion were in the same direction as occurred during the cortisol infusion, but were not significant. These results suggest that cortisol has a sleep modulatory effect. The decrease in REM sleep during the ACTH infusion may be mediated by the rise in endogenous cortisol. However, ACTH specifically altered sleep, in that it inhibited the cortisol-induced increase in SWS. Peripherally administered CRH had no intrinsic influence on sleep.

Effects of toluene exposure on the spontaneous cortical activity in rats

Effects of toluene on the electroencephalogram (EEG) and its power spectra were measured during a 2-hr exposure in a dynamic inhalational chamber in rats. Rats were exposed to one of six graded concentrations (110.6, 162.5, 432, 676, 1558, 2730 ppm) of toluene on different days. It was found that the duration of waking (W) was increased with a decrease in duration of rapid eye movement (REM) sleep even at 110.6 ppm. Duration of nonrapid eye movement (NREM) sleep was decreased with an increase of W and a decrease of REM sleep at 162.5 ppm. Dose-related effects were noted in higher concentrations. The power of δ frequency band was increased with a decrease of θ frequency band power at hr 1 of exposure to 676 ppm during REM sleep recorded from the visual cortex. The power of θ frequency band was also decreased at hr 2 of exposure at 432 ppm. During W and NREM sleep power spectra were not changed significantly. Results indicate that the changes of EEG are a sensitive measure of the effects of toluene on the central nervous system (CNS).

Hypnotic action of flunitrazepam in the rat: Does 5-HT mechanism play a role?

This study examined whether pharmacological manipulation of serotonergic (5-HT) systems would affect the hypnotic action of flunitrazepam in rats. Flunitrazepam, a potent hypnotic, was used alone or combined with parachlorophenylalanine (pCPA), an inhibitor of the synthesis of 5-HT, 8-OH-DPAT, a 5-HT 1A receptor agonist and fluvoxamine, an inhibitor of the reuptake of 5-HT. Flunitrazepam increased the amount of orthodox sleep, the latency of rapid eye movement (REM) sleep and decreased the amount of REM sleep. The drug pCPA decreased the total sleep time and the amount of orthodox and REM sleep. Administration of flunitrazepam to pCPA-pretreated rats induced orthodox sleep in an identical way to that found in the controls. The drug 8-OH-DPAT increased wakefulness and the latency of REM sleep. The association of flunitrazepam with 8-OH-DPAT abolished the increase in waking seen after 8-OH-DPAT alone. In contrast, the combined treatment with flunitrazepam and 8-OH-DPAT resulted in a lengthening of the latency of REM sleep significantly greater than that observed with the same dose of each drug alone. Fluvoxamine increased the latency and decreased the amount of REM sleep. The association of fluvoxamine with flunitrazepam induced a decrease in REM sleep, equal to the sum of the effects of the two drugs alone. Fluvoxamine did not modify the other effects of flunitrazepam. The present experiments demonstrate that the association of pCPA, 8-OH-DPAT and fluvoxamine, did not alter the hypnogenic effect of flunitrazepam. The possibility of an involvement of 5-HT mechanisms in the effect of flunitrazepam on the phasic events in sleep is questionable.

Decreases in REM sleep after phentolamine depend on the ambient temperature

According to monoaminergic theories of rapid-eye-movement (REM) sleep, phentolamine (PHEN), an α-adrenoceptor antagonist that diminishes noradrenergic activity, should decrease REM sleep. However, PHEN also causes a fall in body temperature (Tb) that depends on the ambient temperature (Ta). When REM sleep and Tb were recorded in the same rats at 4 Ta's, after intraperitoneal injections of either PHEN or saline, the two measures were highly correlated. When PHEN lowered Tb, at Ta 20°C, latency to REM sleep increased and total REM time decreased compared to controls. At Ta 32°C, where PHEN had no effect on Tb, drug-treated rats had as much REM sleep as did controls.

Continuous pontine cholinergic microinfusion via mini-pump induces sustained alterations in rapid eye movement (REM) sleep

Although there is much evidence that single microinjections of cholinomimetics into the pontine reticular formation (PRF) evokes rapid eye movement sleep (REMS), no study has yet demonstrated whether protracted manipulations of PRF cholinergic levels can produce sustained alteration of this sleep state. In this study, in rats, an indwelling, chronically implanted osmotic mini-pump was used to infuse carbachol, scopolamine, or saline solutions into various brainstem regions or the fourth ventricle for a period of five consecutive days. Throughout the period of pump operation, carbachol infusions chiefly in the PRF produced sustained REMS augmentation primarily during the night cycle, whereas scopolamine produced a sustained decrease in REMS primarily during the day cycle. The findings provide considerable support for a PRF cholinergic hypothesis of REMS generation and regulation and suggest that the alterations in REMS result from a muscarinic receptor mediated change in PRF neuronal activity.

Cessation of thermoregulation during REM sleep in the pocket mouse.

Electrophysiological sleep patterns, respiration frequency, brain temperature (Tbr), and ear temperature (Tear) were recorded from five pocket mice (Perognathus longimembris) exposed to ambient temperatures (Ta) of 22.5, 27.5, 32.5, and 35.0 degrees C. Thermoregulation was curtailed during rapid-eye-movement (REM) sleep, since Tbr declined following REM onsets at Ta's below thermoneutrality and increased at Ta's above thermoneutrality. Tbr subsequently returned to pre-REM levels following the termination of each REM episode. Respiratory frequency was inversely related to Ta but not as strongly during REM sleep as during slow-wave sleep (SWS). These results confirm previous reports of loss of thermoregulatory ability during REM sleep. Mean duration and proportions of wakefulness, SWS, and REM sleep were unaffected by Ta, consistent with earlier findings on ground squirrels, but differing from reports of decreased REM sleep in nonhibernators. Hibernators may have lower peripheral thermosensitivities than nonhibernators, facilitating sleep at low ambient temperatures and during entrance into hibernation.

Effects on sleep of phentolamine and epinephrine infused into the locus coeruleus of cats

The sleep-wavefulness behavior of cats was studied after infusion of phentolamine (3 μg, bilateral) or epinephrine (60 μg, bilateral) into the locus coeruleus. The drugs exerted opposite effects: phentolamine increased rapid eye movement (REM) sleep and decreased light slow wave sleep; epinephrine decreased REM sleep, increased rapid eye wave sleep and augmented wakefulness. The REM-enhancing effect of phentolamine was due to more REM periods than in control experiments, with a shortening of the sleep cycle. Epinephrine, by contrast, resulted in fewer REM periods and a prolongation of the sleep cycle. The data support the hypothesis that pontine catecholamines inhibit REM sleep and facilitate wakefulness in cats, and implicate the rostral pons as an important site for the REM-increasing effect of systemically administered phentolamine.

Demonstration of ponto-geniculo-occipital waves in the albino rat

Monophasic waves that resemble the ponto-geniculo-occipital (PGO) waves recorded in cats were electrophysiologically recorded in the albino rat. These waves were most prominent within rapid eye movement (REM) sleep episodes and in the segments of slow-wave sleep just preceding both REM sleep periods and spontaneous awakenings. Administration of para-chlorophenylalanine (300 mg/kg) caused a change in distribution of the waves—an increase in the proportion occurring in waking and a decrease in REM sleep. REM sleep deprivation carried out by hand awakenings caused an increase in the proportion of waves occurring prior to REM sleep onset as well as a decrease in the proportion of waves in REM sleep. The waves recorded in the albino rat were so similar in their appearance to the PGO waves recorded in the cat as well as in their temporal distribution, and susceptibility to manipulation, that this activity appeared to constitute the rat homolog of PGO waves.

Effect of tryptophan on sleep in the rat

Rats implanted with EEG and EMG electrodes were injected intraperitoneally with 30 or 120 mg/kg of l-tryptophan and a recording was made for 6 hr. The 30 mg/kg dose decreased the latency to the first slow-wave sleep (SWS) episode by 15 min (43%) and to the first rapid eye movement (REM) sleep episode by 18 min (27%). There were no changes in wakefulness. SWS or REM sleep during the 6hr of EEG recording. In contrast, the 120 mg/kg dose did not affect sleep latencies but increased wakefulness and decreased REM sleep during the second hour of EEG recording. The reduction of SWS latency produced by the 30 mg/kg tryptophan occurred at a time when the level of 5-hydroxyindoleacctic acid (5-HIAA) was elevated in the cortex and pons-medulla (i.e. 15 min post-injection). At the same time, hippocampal and cortical dopamine levels decreased while that of homovanillic acid did not change. The level of norepinephrine, also, decreased in the hippocampus. Whereas these changes in brain calecholamines were not observed 45 min after tryptophan administration, there was an elevation of 5-hydroxytryptamine in the pons-medulla and cortex as well as of 5-HIAA in the pons-medulla and hippocampus. Present data suggest that the hypnotic effect of tryptophan may involve the normal sleep mechanism, since similar neurochemical findings were reported during natural SWS. However, the effect may be limited to a certain dose range because a high dose produced waking rather than sleep.

LSD and tryptamine effects on sleep/wakefulness and electrocorticogram patterns in intact cats

Effects of intravenous infusions of LSD (3.75, 7.5, 15 microgram/kg over 5 min; crossover N = 4) and tryptamine (0.04, 0.08, 0.12 mg/kg/min for 150 min; crossover N = 6) were compared to saline in intact cats through observation of five sleep/waking patterns. Electrocorticogram (ECoG) was analyzed for frequency band indices and mean amplitude and frequency. LSD increases wakefulness and drowsiness and decreases spindle sleep and rapid eye movement (REM) sleep during the first 75 min (period 1). The increase in active wakefulness and decrease in REM sleep persist during period 2, with an increase in spindle sleep thereafter. LSD increases delta index and ECoG amplitude, with a decrease in ECoG frequency; these effects peaked in period 2. Tryptamine increases wakefulness and drowsiness during period 1, with decreases in spindle sleep and REM sleep. The increase in quiet wakefulness and decrease in REM sleep persist during period 2, but no significant tryptamine effect is seen in sleep/waking patterns after infusion ceases. ECoG frequency increases during tryptamine infusion (periods 1 and 2), while ECoG amplitude increases during periods 2 and 3. Thus LSD and tryptamine both increase wakefulness, decrease spindle sleep, and decrease REM sleep.

Effects of prolonged bed rest on EEG sleep patterns in young, healthy volunteers

The bed-rest study involved eight subjects, 18–24 years of age, and was divided into control, experimental (bed-rest, BR), and recovery phases of 5,5 and 6 weeks, respectively. During the bed-rest period, four subjects continued to exercise on the total body ergometer while confined to bed, while the remainder acted as controls (without exercise). All subjects, except for the controls during the bed-rest period, performed 600 kcal of exercise a day. Subjects were paired and recorded together: 1 and 8; 2 and 7; 3 and 6; 4 and 5. This grouping remained the same throughout the study. A total of 5 recordings were made: 1 during baseline, 2 during bed rest (BR 1 and BR 2) and 2 during recovery. Baseline mean percentages of total night sleep were: rapid eye movement (REM)=24.64; Stages 1+2=58.95; Stages 3+4=16.44; and Stage 4=4.62. A Mann-Whitney U test (two-tailed) was performed on all data. A significant increase ( P<0.01) in deep sleep (Stages 3+4) and a decrease ( P<0.005) in light sleep (Stages 1+2) for the entire group (non-exercise, NE, and exercise, E) is seen when the entire BR period is combined (Table I, BR 1 + BR 2) and compared to baseline values. There was no significant change in REM, although there was a tendency in the NE group for decreased REM sleep. With recovery (R 1 + R 2), the increase in deep sleep remains but is not, significant ( P>0.05; <0.1) as is the decrease in light sleep, relative to baseline values. However, Stage 4 for the entire group showed a significant ( P<0.05) increase during bed rest (BR 1 + BR 2) and recovery (R 1 + R 2) relative to baseline values. When E and NE (Table II) are compared separately during bed rest to baseline values for deep sleep (Stages 3+4), only the NE group shows significant differences ( P<0.05), although there is a progressive increase in deep sleep for the E group over the bed-rest period.

Sleep in patients with Parkinson's disease and normal subiects prior to and following levodopa administration

Six patients with parkinsonism and 4 spouse control subjects were studied in the sleep laboratory prior to administration of levodopa and during initial, short‐term, long‐term, and chronic usage. The parkinsonian patients had a significant amount of sleeping difficulty, taking much longer to fall asleep and awakening frequently for long periods during the night, as compared with spouse control subjects and a normal, elderly control group. Values for rapid eye movement (REM) sleep were similar to those of both control groups, while Stage 3 sleep was decreased. Three of the 6 patients showed a decrease in REM sleep with initial drug administration at the 1.0 Gm. per day dosage level. One had a marked increase in REM sleep for about the first 2 weeks of drug administration. However, REM sleep values for all patients with long‐term and chronic drug administration were similar to base‐line values. In the spouse control subjects, other than a slight increase in REM sleep with initial drug administration which was not maintained with long‐term use, no changes were noted in REM sleep, even during withdrawal of the drug. In both patients and control subjects, values for sleep induction and sleep maintenance were essentially unaltered by the administration of levodopa. Biochemical implications of these data are discussed. In addition, the clinical implications in terms of evaluating and treating the moderately severe insomnia in parkinsonian patients are described.