Eur J Appl Physiol (1992) 64:371-376

Met-enkephalin, -endorphin and cortisol responses to sub-maximal exercise after sleep disturbances

European Applied Journal o f

Physiology and Occupational Physiology © Spnnger-Verlag 1992

F. Mougin 1,2, M. L. Simon-Rigaud 1, C. Mougin 3, H. Bourdin 1, M. C. Jacquier 4, M. T. Henriet 5, D. Davenne 2, J. P. Kantelip i, p. Magnin 1, and R. C. Gaillard 4

Service de Physiopathologie Respiratoire et C~r~brale, M~decine et Biologie du Sport, CHU F-25030 Besan~on Cedex, France 2 Laboratoire d'Etudes et de Recherches sur la Performance Sportive, UFR-STAPS, BP 138, F-21004 Dijon Cedex, France 3 Laboratoire de Virologie, CHU F-25 030 Besan~on Cedex, France 4 Clinique M~dicale, H6pital Cantonal Universitaire, CH-1211 Gen~ve, Switzerland 5 Laboratoire d'Explorations Fonctionnelle, M~taboliques et R6nales, CHU F-25 030 Besan~on Cedex, France

Accepted December 9, 1991

Summary. The present study compared the effects of partial sleep deprivation and the effects of an intake of a hypnotic compound (zolpidem) prior to bedtime, on sleep and on hormonal and metabolic adaptations to subsequent exercise. Sleep deprivation consisted of a delayed bedtime and an early getting-up time. Eight young subjects, who slept well and were highly trained athletes, were enrolled in this study. Sleep was recorded polygraphically and the following afternoon exercise was performed on a cycle ergometer for 30 min at 75% of maximal oxygen consumption (VO2max) after a 10- min warm up. Met-enkephalin, fl-endorphin, cortisol, and lactate concentrations were measured at rest and during exercise. The data obtained after experimental sleep, with and without medication were compared with those obtained in the reference condition with nor- mal sleep. Both types of sleep reduction decreased the total sleep time, stage 2 sleep, and rapid eye movement sleep, whereas zolpidem administration did not modify either the duration of sleep or the sleep stages. After the reference night, plasma met-enkephalin did not show any significant change at the end of the submaximal ex- ercise, whereas fl-endorphin, cortisol, and lactic acid concentrations increased significantly in all subjects. The changes in concentration in fl-endorphin were sig- nificantly related to the changes in cortisol (r=0.78; P<0.01) and to the changes in plasma lactic acid (r=0.58; P<0.05). Cortisol concentrations were also related to lactic acid values (r=0.94; P<0.01). Partial sleep loss altered lactate concentrations during sub- maximal exercise but did not affect the hormonal levels of met-enkephalin, fl-endorphin and cortisol in the blood. Zolpidem administration failed to change lac- tate and hormone concentrations. These results sug- gested that partial sleep deprivation may have contrib- uted to the changes in metabolic responses without sig- nificantly altering the hormonal response to exercise. Zolpidem intake did not impair the response of differ- ent variables to exercise the following day.

Offprint requests to: F. Mougin

Key words: Sleep - Zolpidem - Met-enkephalin - fl-En- dorphin - Cortisol - Lactate

Introduction

A number of circumstances in the lives of athletes caus- ing them either to rise very early or to delay bedtime, or midnight insomnia may result in disrupted sleep sched- ules. Among these circumstances, several are frequently encountered, i.e. time zone changes after transmeridian flight, early start of an endurance event, changes in en- vironment, all factors which may increase fatigue and produce anxiety before a major competition. These fac- tors may be potent agents of stress and may lead ath- letes to use hypnotic and/or anxiolytic compounds to improve their nocturnal sleep. In these situations, ques- tions arise: is it better to be deprived of sleep or to take a hypnotic medication so that the physiological stress of subsequent exercise is not exaggerated, and optimal performance is achieved? Previous studies have de- monstrated that exercise stress increases plasma con- centrations of fl-endorphin and cortisol (Brooks et al. 1988; Buono et al. 1986; Colt et al. 1981; Donevan and Andrew 1987) although conflicting evidence exists con- cerning the release of met-enkephalin during exercise (Farrell et al. 1987; Howlett et al. 1984; Jaskowski et al. 1989; Mougin et al. 1987). In addition, the secretory pattern of these different hormones has been shown to be driven by several different mechanisms-circadian and ultradian rhythms and sleep phenomena (Born et al. 1986). To our knowledge, there are few reports which have examined the influence of disturbed sleep on these hormonal responses to subsequent exercise (Martin et al. 1986; O'Connor et al. 1991). The purpose of this investigation was to evaluate the effects of two different conditions of limited sleep compared to ordi- nary 8-h sleep and the effects of zolpidem-induced sleep on endogenous opioid and cortisol response to subsequent submaximal exercise in physically highly trained subjects.

372

Methods

Subjects. Eight healthy athletes [mean age 24 (SEM 0.8) years; mean body mass 71.5 (SEM 1.8) kg] who normally did not take afternoon naps, volunteered to take part in this study. They were all informed about the protocol and signed consent forms. They were selected by means of a sleep questionnaire on their chrono- biology (Home and ()stberg 1976) and on their maximal oxygen uptake ([702max)- The mean estimated sleep duration was 8 h (SEM 0.4) and their time of going to bed varied between 9.30 p.m. and 11 p.m. Their I;'O2~ax measured directly during a triangular exercise as has previously been described (Mougin et al. 1991) av- eraged 63.5 (SEM 3.8) ml .kg- l .min -1. The subjects did not re- port any habitual sleep disturbances and drank and smoked little. None of them was taking drugs, including opioid medications or hormones.

Protocol. The experimental protocol has been previously reviewed and approved by an Ethics Committee for the protection of hu- man subjects. A randomized, double-blind, cross over protocol was employed with four sleep conditions, using either placebo, 10 mg of zolpidem (Laboratories Synthelabo, Plessis-le Robinson, France) or a partial sleep loss either by a delayed bedtime or an early getting-up time.

Sleep design. The sleep design used in the present experiment has been described in part elsewhere (Mougin et al. 1991). The sub- jects slept in a sleep laboratory, always in the same sound-atte- nuated room throughout the study. They attended the sleep labo- ratory on a total of 6 nights, arriving at about 8.30 p.m. to prepare for polysomnographic recording. The electro-encephalograms (EEG) were recorded from scalp electrodes fixed with collodion at the following sites: two temporal (T3 and T4), two occipital (O1 and O2), two fronto-temporal (FP1 and FP2) and one vertex (Cz), to dispose of two spare electrodes. Eye movements were recorded from two electrodes placed at the inner and outer corners of one eye and electromyograms (EMG) from two chin electrodes. Each EEG was recorded on three channels using two bipolar montages (occipital vertex, temporal vertex and fronto-temporal vertex) and both EMG and electro-oculogram (EOG) on a single channel. The period of time separating the different nights was between 5 and 7 days. The recording sessions were as follows: 1. A reference night preceded by a habituation night during which lights were turned off from about 10.30 p.m. to about 07.00 a.m. 2. On the 2 medication-induced nights 10 rain before bedtime the subjects took their assigned capsule which contained either 10-mg zolpidem or placebo. Lights were turned off at about 10.30 p.m. and on again at about 7 a.m.

Throughout the 4 different nights, the polygraphic records were monitored continuously at a paper speed of 15 mm. s-1. 3. A sleep-deprived night during which the subjects were not al- lowed to sleep before 3 a.m. and then were awakened at 7 a.m. 4. A sleep-deprived night during which the subjects went to bed at 10.30 p.m., were awakened at 3 a.m. and were not allowed to sleep thereafter.

During the sleep deprivation periods, the subjects were kept awake by passive means such as reading books or watching televi- sion. They were not permitted to take food, caffeine or stimulants and were under the continuous observation of a technician during this time. Polygraphic records were only made during the time spent in bed.

All the sleep records were coded and scored blind according to the Rechtschaffen and Kales classification (1968). The data were analysed by computer giving total sleep time, sleep onset la- tency and the duration of different sleep stages.

Exercise protocol. After each experimental night, the subjects exer- cised on a cycle ergometer (Siemens S.A., Saint Denis, France) at 2 p.m. as previously described (Mougin et al. 1991), with minor modifications. The protocol consisted of a 10-min warm-up pe-

riod followed by a period of 30 min at a steady intensity corre- sponding to 75% of predetermined I202 . . . . Before each trial, a catheter was inserted into a superficial forearm vein. Blood sam- ples for hormone concentrations were obtained at rest and at the end of the submaximal exercise, and those for lactate concentra- tions were obtained at rest, following the warm-up period, and during the steady-state submaximal exercise. Blood samples were immediately placed on ice and centrifuged within 10min at 3000 rpm at 4 ° C. The plasma was removed and placed in a freezer at - 7 5 ° C until assayed. The fl-endorphin immuno-reac. tivity [C-terminal B-(LPH)] was detected after plasma extraction by radio-immunoassay using an antiserum showing equimolar cross reactivity with fl-LPH (Jeffcoate et al. 1978). Samples for met-enkephalin analysis were prepared in the same way, except that the tubes contained trasylol (aprotinin 1000 KJU. min-1) and that the plasma was decanted into tubes containing glycine-HC1 solution. Met-enkephalin was assayed by oxidizing the samples with H202 after extraction and using an antiserum with high spe- cificity for met-enkephalin sulphoxide (Clement-Jones et al. 1980). With these methods, the intra-assay and interassay coeffi- cients of variation were 8% and 15% for ~-endorphin, and 9% and 12% for met-enkephalin. Radio-immunoassay for cortisol was per- formed using a gamma-coat (1251) RIA kit (Clinical Assays, Amer- sham Laboratories, Les Ulis, France). Lactic acid was assayed by an enzymatic UV-method (Boehringer Mannheim GmbH Diag- nostica, Boehringer Mannheim, Meylan, France).

Statistical analysis. All values are given as mean and SEM. A mul- tifactorial analysis of variance was used for statistical analysis of both sleep and exercise data. If significant differences appeared, the Student's t-test was used. The level of significance was P < 0.05.

Polysomnographic data concerning experimental nights and data concerning hormonal and metabolic responses to exercise were compared to those obtained during and after the baseline night. The subjects served as their own controls.

Results

Night-time results (sleep polyoraphy)

Table 1 shows some s leep p a r a m e t e r s r e c o r d e d du r ing the re fe rence a n d e x p e r i m e n t a l nights . The d i s t u r b e d n ights a f fec ted the c o m p o s i t i o n o f s leep c o m p a r e d to tha t o b s e r v e d dur ing n o r m a l s leep. The s leep onse t la- tency , wh ich was ca l cu l a t ed f rom l igh ts -ou t unt i l the first a p p e a r a n c e o f s tage 2, was s ign i f i can t ly r e d u c e d b y the la te r b e d t i m e as c o m p a r e d to the con t ro l (P<0 .05 ) . I t was u n c h a n g e d by the ear ly ge t t i ng -up t ime. The du- r a t ion o f s tage 1 s leep dec rea sed af te r a la te b e d t i m e bu t no t af ter ear ly rising. Both pa r t i a l s leep dep r iva - t ions d e c r e a s e d the to ta l s leep t ime (TST; P < 0.01), the d u r a t i o n o f s tage 2 s leep ( P < 0.01) and the d u r a t i o n o f r a p i d eye m o v e m e n t ( R E M ) s tage s leep (P<0 .01 ) . A m o u n t s o f s tages 3 and 4 s leep were no t a l t e red by a l ack o f sleep. Z o l p i d e m d id no t change e i ther the s leep onse t l a t ency or TST. It d id not af fec t the d u r a t i o n o f d i f fe ren t s leep stages.

Exercise results

The exerc ise c o n d u c t e d af ter n o r m a l s leep was asso- c ia ted wi th u n c h a n g e d p l a s m a m e t - e n k e p h a l i n and wi th an inc rease in p l a s m a f l - e ndo rph in concen t r a t i ons

373

Table 1. Sleep values for the reference night, for the nights under placebo and zolpidem and for the nights of both conditions of reduced sleep (delayed bedtime and early getting-up time): time spent in the different stages of sleep

n = 8 Reference night Placebo night Zolpidem night Delayed bedtime Early getting-up (min) (min) (min) (min) time (min)

mean SEM mean SEM mean SEM mean SEM mean SEM

Sleep onset latency 14.7 3.6 13.7 3.5 12.6 2.8 4.6 0.9* 12.6 2.9 Total sleep time 456.2 9.3 462.0 3.6 465.3 7.6 250.0 9.1"* 255.1 7.6** Stage 1 sleep 8.2 5.4 15.9 7.6 18.2 8.0 4.8 3.0* 17.8 10.1 Stage 2 sleep 310.8 16.4 289.5 13.1 294.5 17.3 160.0 16.2"* 166.0 11.1"* Stage 3 sleep 24.8 3.7 33.5 3.8 39.3 7.8 22.6 2.2 18.6 1.6 Stage 4 sleep 40.1 7.1 37.0 8.6 32.6 7.2 31.3 7.8 26.4 5.7 Stage REM sleep 69.2 8.7 87.8 13.7 81.8 7.9 34.7 7.9** 27.6 7.7**

REM, rapid eye movement; * P < 0.05; ** P < 0.01 compared with the values obtained after reference night

Table 2. Met-enkephalin, fl-endorphin and cortisol concentrations obtained at rest and at the end of steady-state exercise after the different experimental nights

n = 8 Met-enkephalin fl- Endorphin Cortisol (pg. m l - i) (pg. m l - 1) (ng. 100 m l - 1)

rest SS 30th min rest SS 30th min rest SS 30th min

mean SEM mean SEM mean SEM mean SEM mean SEM mean SEM

After reference night 66.0 8.8 86.5 19.9 25.7 7.4 67.0 15.6 18.9 2.4 25.7 2,1 After placebo night 72.6 10.0 77.2 13.0 32.3 11.8 82.7 24.3 17.9 1.2 25.2 2.9 After zolpidem night 85.7 14.4 82.3 20.4 24.6 5.9 49.3 7.9 20.1 2.0 24.0 1.9 After delayed bedtime 94.1 19.5 60.1 5.2 23.3 4.5 97.2 50.2 18.1 2.3 24.5 3.0 After early getting-up time 65.1 9.1 61.1 9.1 22.8 3.8 90.6 35.6 16.3 2.0 23.7 1.5

* P < 0.05; ** P < 0.01 at the 30th min of steady-state (SS) compared with the resting values

8 I

- ' . 6 ~ O E

,~4 I-- O

t ~ O 0 2 a n

~-~. • ~

REST WARM UP SS 10 min SS 20 min SS 30 min

..<

Fig. 1. Blood lactate concentra- tions (mean and SEM; n = 8 ) ob- served at rest, at the end of warming-up, at the 10th, 20th and 30th min of the submaximal exer- cise. * P < 0.05 compared with the values obtained after a reference night. SS, steady state. [] refer- ence night; [] placebo night; [] zolpidem night; [] delayed bed- time; • early getting-up time

at the end of steady power output compared to the rest- ing values (P<0.01; Table 2). As with the changes ob- served in plasma fl-endorphin concentrations, submaxi- mal exercise cortisol concentrations were significantly elevated (P<0.05) (Table 2). A marked increase in blood lactic acid concentration during the steady-state exercise was also observed in all athletes when com- pared with resting data (Fig. 1). The lactate values were around the 4mmol.1-1 level throughout the steady-

state cycling. At the end of the steady-state exercise in the reference condition, significant correlations were found between plasma concentrations of fl-endorphin and cortisol (r=0.78; P<0.01) and between the fl-en- dorphin and lactic acid concentrations (r=0.58; P< 0.05). Submaximal cortisol concentrations also cor- related with the corresponding lactate concentrations (r=0.94; P<0.01). The resting values of plasma met- enkephalin, fl-endorphin, cortisol, and lactic acid con-

374

centrations were similar in the three experimental con- ditions compared to those observed after the control and the placebo nights. The exercise performed after the experimental nights also led to an increase in fl-en- dorphin and cortisol concentrations similar to those ob- served in the control situations. Partial sleep loss signif- icantly exaggerated the increase in lactate concentra- tions at the end of the warm-up and during all submax- imal exercise measurements (Fig. 1), whereas zolpidem administration did not affect the lactate concentrations (Fig. 1).

Discussion

After normal sleep schedules, plasma fl-endorphin, cor- tisol, and lactic acid concentrations increased at the end of the steady-state cycling period whereas no changes occurred in plasma met-enkephalin concentra- tions. The fl-endorphin increase observed in this study was in agreement with other reports (Fraioli et al. 1980; Goldfarb et al. 1990; Hoffmann 1990; Rahkila et al. 1987) and was probably due to a release from the ante- rior pituitary in parallel with adrenocorticotrophic hor- mone (ACTH); (Guillemin et al. 1977) for which the plasma cortisol provided a valuable index of pituitary secretion. Previously, some studies (Langenfeld et al. 1987) have shown that strenuous exercise stimulates an increase in fl-endorphin to a greater extent than a mild intensity exercise (lower than 60% of ~)'O2max ). Some authors (Farrell et al. 1983; De Meirleir et al. 1986; Schwartz and Kindermann 1990) have indeed demon- strated that exercise-induced elevation of circulating fl- endorphin only occurs after lactic acid concentrations have exceeded a threshold of 4 mmol. 1-1.

Our results agreed with these observations. The in- tensity of imposed exercise (75% of l?O2max) on our athletes, together with the concentrations of plasma lac- tic acid around 4 mmol.1-1 may be the major factor in releasing fl-endorphin in the blood stream. Furthermore it has been well documented that cortisol concentra- tions are related to the intensity of exercise (Kuoppal- salmi et al. 1980; Kraemer et al. 1989). Indeed in some studies, the intensity of exercise may be too low to elicit a response from the adrenal gland. In our design, all our athletes showed an increase in plasma cortisol re- lated to lactic acid suggesting that lactic acid may stim- ulate the cortisol secretion (Farrell et al. 1983). More- over, cortisol concentrations correlated with fl-endor- phin concentrations, which agreed with previous obser- vations, in which the more elevated values of both hor- mones have been shown to occur after the higher inten- sity of exercise (Dearman and Francis 1983; Strassman et al. 1989).

The study of plasma met-enkephalin is of great in- terest since very few observations are available. Kraemer et al. (1990) have demonstrated an increase of plasma pro-enkephalin peptide F concentrations in re- sponse to exercise at 75% of VO2max conducted at sea level. Several authors have observed a lack of met-en- kephalin response following a training programme

(Howlett et al. 1984) or in trained subjects (Farrell et al. 1982; Mougin et al. 1987). The lack of met-enkephalin response to exercise in the present study might have been related to the training state of our subjects. The very rapid degradation of this peptide in peripheral plasma (Rossier and Chapouthier 1982) may also have been another cause of the lack of plasma met-enke- phalin changes. Nevertheless, the responses of the cen- tral nervous system opioid peptides to our imposed ex- ercise are unknown. The involvement of fl-endorphin and met-enkephalin in the central nervous system is a matter of speculation.

The question arises as to whether partial sleep depri- vation and drug-induced sleep influence normal sleep patterns and exercise-induced hormonal changes. In both deprived sleep nights, the sleep deficit and the length of wakefulness were about the same with, how- ever, a different pattern between the sleep reduced nights. The delayed bedtime led to a shorter sleep onset latency and a decrease in the amount of stage 1 sleep, whereas getting up earlier did not modify these sleep parameters. However, both sleep losses resulted in a smaller total sleep time and in a decrease of the amounts of stage 2 and REM sleep compared to the control night. These results are in agreement with pre- vious sleep investigations which have demonstrated dif- ferent sleep patterns when sleep is partially reduced. Studies on early rising and delayed bedtime with a 2-h sleep reduction (Clodore et al. 1987), 3-h sleep loss (Taub and Berger 1976), and with some weeks of 2 h sleep reduction (Horne and Wilkinson 1985) have shown the same sleep characteristics as with our pres- ent delayed bedtime, and in addition, more slow wave sleep (SWS). In contrast with these studies, we did not observe any changes in the duration of SWS. These dis- crepancies might be due to methodological differences involving the duration of sleep loss and/or the selec- tion of our subjects who were highly trained athletes, and other types of sleepers according to the classifica- tion of Home and Ostberg (1976). It has been well doc- umented that athletes' sleep patterns are different from sedentary people, with greater amounts of SWS being necessary for their physical recovery (Home 1981). Therefore, we would suggest that, during a sleep de- prived night, the duration of SWS did not increase at the expense of stage 2 sleep. Indeed, in our study sleep reduction resulted in a decrease in stage 2 sleep. These results may be compared with our previous observa- tions (Mougin et al. 1991) in which we also reported a lower percentage of stage 2 sleep when athletes were sleep deprived in the middle of the night. Most studies have reported that the SWS serves in the restorative processes for physical fatigue and REM sleep for the function of the central nervous system; however, the role of stage 2 sleep remains poorly defined. We may suppose that insufficient stage 2 sleep each night af- fects physical performance the following day. Zolpi- dem-induced sleep changed neither the sleep onset la- tency nor total sleep time; nor did it affect the duration of different sleep stages. These results were in agree- ment with most studies which have exhibited no effect

375

of the administrat ion of 10-mg zolpidem on sleep (for review see Morselli et al. 1988).

It is noteworthy that our results showed that sleep loss or zolpidem-induced sleep failed to alter the hor- monal responses to subsequent submaximal exercise. In a previous study, Opstadt et al. (1980) have reported higher cortisol concentrations measured on day 3 and lower cortisol concentrations on day 5 of a course of 107 h of continuous activity with less than 2 h of sleep, combined with an energy deficit. O 'Connor et al. (1991) have observed a decrease or an increase of salivary cor- tisol concentrations after swimming 183 m at an inten- sity equal to 90% of the maximal velocity, conducted after sleep disturbances caused by air travel across four t ime zones. However, the changes in cortisol concentra- tion were due to a 4-h advance or delay in relation to the circadian phase. In addition, Martin et al. (1986) did not find any evidence of altered fl-endorphin and cortisol concentrations during 3 h of mild exercise after a prolonged loss of sleep or during a 30-min exercise period at 65% l?O2max after 2 nights of broken sleep. This lack of agreement requires further investigation, since the experimental protocols were dissimilar. How- ever, we would suggest, as did Martin et al. (1986), that the hormonal responses, which are considered to be an index of the physiological stress imposed by exercise, are unchanged by sleep loss.

After both the sleep loss conditions, the only change observed was a higher lactate concentrat ion that reached values over 4 m m o l - 1 - 1 at the end of the warm-up period and underwent an upward drift until the end of the per iod of steady-state exercise. To our knowledge, few studies have taken into account the changes in this metabol ic variable in response to exer- cise after sleep loss. In contrast to our study, McMur- ray and Brown (1984) have demonstrated lower con- centrations of b lood lactate during submaximal exer- cise at 80% of the lfrO2max following a 24-h sleep loss. These authors have suggested that their results reflected the morning activity to maintain a wakeful state, which caused a greater turnover of lactate. The higher lactate concentrations observed in the present study following sleep deprivat ion might have been due to a decrease in mechanical efficiency. However, in a recent study using the same experimental protocol, no differences in sub- maximal exercise oxygen uptake and heart rate were found between sleep deprived and non-sleep deprived conditions (Mougin et al. in press). Nevertheless, this increase in lactate concentrations might not have been sufficient to lead to a significant enhancement of fl-en- dorphin and cortisol concentrations after both types of sleep deprivation.

Zolp idem administered as a single dose did not af- fect either hormonal or metabolic responses at rest or during exercise. No reported study has examined the influence of this new imidazopiridine (zolpidem) on physical per formance following its use. The only stud- ies conducted on this compound have essentially only shown the daytime residual effects of zolpidem on psy- chomotor performance. Our results would confirm that zolpidem up to a dose of 20 mg can be considered as

totally free of residual effect in a popula t ion of young adult volunteers (Morselli et al. 1988).

In summary, the results of the present study indi- cated that neither sleep deprivation nor zolpidem-in- duced sleep influenced the secretion of met-enkephal- in, fl-endorphin, and cortisol during subsequent sub- maximal exercise.

Acknowledgements. The authors thank the subjects for their en- thusiastic efforts, Dr. G. Toubin, Prof. S. Berthelay and the tech- nicians for their valuable assistance in conducting the radio-im- munoassay. The help of Prof. Lavoie is gratefully acknowledged.

References

Born J, Kern W, Bieger K, Fehm-Wolfsdorf G, Schiebe M, Fehm HL (1986) Night-time plasma cortisol secretion is associated with specific sleep stages. Biol Psychiatry 21 : 1415-1424

Brooks S, Burrin J, Cheetham ME, Hall GM, Yeo T, Williams C (1988) The responses of the catecholamines and fl-endorphin to brief maximal exercise in man. Eur J Appl Physiol 57:230- 234

Buono M J, Yeager JE, Hodgdon JA (1986) Plasma adrenocortico- tropin and cortisol responses to brief high-intensity exercise in humans. J Appl Physiol 61:1337-1339

Clement-Jones V, Lowry PJ, Rees LH, Besser GM (1980) Met- enkephalin circulates in human plasma. Nature (Lond) 283:295-297

Clodore M, Benoit O, Foret J, Touitou Y, Touron N, Bouard G, Auzeby A (1987) Early rising or delayed bedtime: which is bet- ter for a short night's sleep? Eur J Appl Physiol 56:403-411

Cold EWD, Wardlaw SL, Frantz AG (1981) The effect of running on plasma fl-endorphin. Life Sci 28:1637-1640

Dearman J, Francis KT (1983) Plasma levels of catecholamines, cortisol and beta-endorphins in male athletes after running 26.2, 6, and 2 miles. J Sports Med 23:30-38

De Meirleir K, Naaktgeboren N, Van Steirteghem A, Gorus F, Olbrecht J, Block P (1986) Beta-endorphin and ACTH levels in peripheral blood during and after aerobic and anaerobic ex- ercise. Eur J Appl Physiol 55:5-8

Donevan RH, Andrew GM (1987) Plasma fl-endorphin immuno- reactivity during graded cycle ergometry. Med Sci Sports Ex- erc 19:229-233

Farrell PA, Gates WK, Maksud MG, Morgan WP (1982) In- creases in plasma fl-endorphin/fl-lipotropin immunoreactivity after treadmill running in humans. J Appl Physiol 52:1245- 1249

Farrell PA, Garthwaite TL, Gustafson AB (1983) Plasma adreno- corticotropin and cortisol responses to submaximal and ex- haustive exercise. J Appl Physiol 55:1441-1444

Farrell PA, Gustafson AB, Morgan WP, Pert CB (1987) Enkephal- ins, catecholamines and psychological mood alterations ef- fects of prolonged exercise. Med Sci Sports Exert 19:347- 353

Fraioli F, Moretti C, Paolucci D, Alicicco E, Crescenzi F, Fortu- nio G (1980) Physical exercise stimulates marked concomitant release of fl-endorphin and adrenocorticotropic hormone (ACTH) in peripheral blood in man. Experimenta 36:987- 989

Goldfarb AH, Bradley D, Armstrong D, Potts J (1990) Plasma beta-endorphin concentration response to intensity and dura- tion of exercise. Med Sci Sports Exerc 22:241-244

Guillemin R, Vargot T, Rossier J, Minick S, Ling N, Rivier C, Vale W, Bloom F (1977) fl-endorphin and adrenocorticotropin are secreted concommitantly by the pituitary gland. Science 197:1367-1369

Hoffmann P (1990) Endogenous opioid effects elicited by muscle activity. An attempt to explain cardiovascular, analgesic and

376

behavioural mechanism of exercise. Department of Physiol- ogy, University of G&eborg, pp 1-59

Horne JA (1981) The effects of exercise on sleep: a critical review. Biol Psychol 12:241-290

Horne JA, t~stberg O (1976) A self assessment questionnaire to determine morningness-eveningness in human circadian rhythms. In J Chronobiol 4:97-110

Horne JA, Wilkinson S (1985) Chronic sleep reduction: daytime vigilance performance and EEG measures of sleepiness with particular reference to practice effects. Psychophysiology 22: 69-78

Howlett TA, Tomlin S, Ngahfoong L, Rees LH, Bullen BA, Skri- nar GS, McArthur JW (1984) Release offl-endorphin and met- enkephalin during exercise in normal women: response to training. BMJ 288:1950-1952

Jaskowski MA, Jackson AS, Raven PB, Caffrey JL (1989) Enke- phalin metabolism: effect of acute exercise stress and cardio- vascular fitness. Med Sci Sports Exerc 21 : 154-160

Jeffcoate WJ, Rees LH, McLoughlin L, Ratter S J, Hope J, Lowry PJ, Besser GM (1978) Beta-endorphin in human cerebrospinal fluid. Lancet II: 119-121

Kraemer WJ, Fleck S J, Callister R, Shealy M, Dudley GA, Mar- esh CM, Marchitelli L, Cruthirds C, Murray T, Falkel JE (1989) Training responses of plasma beta-endorphin adreno- corticotropin and cortisol. Med Sci Sports Exerc 21:146-153

Kraemer WJ, Dziados JE, Gordon SE, Marchitelli LJ, Fry AC, Reynolds KL (1990) The effects of graded exercise on plasma proenkephalin peptide F and catecholamine responses at sea levels. Eur J Appl Physiol 61:214-217

Kuoppasalmi K, Naveri H, Harkonen M, Adlercreutz H (1980) Plasma cortisol, androstenedione, testosterone and luteinizing hormone in running exercise of different intensities. Scand J Clin Lab Invest 40:403-409

Langenfeld ME, Hart LS, Kao PC (1987) Plasma beta-endorphin responses to one hour bicycling and running at 60% I702 . . . . Med Sci Sports Exerc 19:83-86

Martin BJ, Bender PR, Chert HI (1986) Stress hormonal response to exercise after sleep loss. Eur J Appl Physiol 55:210-214

McMurray RG, Brown CF (1984) The effect of sleep loss on high intensity exercise and recovery. Aviat Space Environ Med 55:1031-1035

Morselli PL, Larribaud J, Guillet Ph, Thiercelin JF, Barthelet G,

Grilliat JP, Th6bault JJ (1988) Daytime residual effects of zol- pidem: a review of available data. In: Sauvanet JP, Langer SZ, Morselli PL (eds) Imidazopyridines in sleep disorders. Labo- ratoires d'Etudes et de Recherches Synth61abo monograph se- ries, vol. 6. Raven Press, New York, pp 379-380

Mougin C, Baulay A, Henriet MT, Haton D, Jacquier MC, Turnill D, Berthelay S, Gaillard RC (1987) Assessment of plasma opioid peptides, fl-endorphin and met-enkephalin at the end of an international nordic ski race. Eur J Appl Physiol 56:281- 286

Mougin F, Simon-Rigaud ML, Davenne D, Renaud A, Garnier A, Kantelip JP, Magnin P (1991) Effects of sleep disturbances on subsequent physical performance. Eur J Appl Physiol 63:77- 82

Mougin F, Simon-Rigaud ML, Davenne D, Bourdin H, Guilland JC, Kantelip JP, Magnin P (1992) Tol6rance ~ l'effort apr6s r6duction de sommeil et apr6s prise d'un hypnotique: le zolpi- dem. Arch Int Physiol Biochim Biophys (in press)

O'Connor PJ, Morgan WP, Koltyn KF, Raglin JS, Turner JG, I(alin NH (1991) Air travel across four time zones in college swimmers. J Appl Physiol 70:756-763

Opstad K, Aakvaag A, Rognum TO (1980) Altered hormonal re- sponse to short-term bicycle exercise in young men after pro- longed physical strain, caloric deficit, and sleep deprivation. Eur J Appl Physiol 45:51-62

Rahkila P, Hakala E, Salminen K, Laatikainen T (1987) Response of plasma endorphins to running exercises in male and female endurance athletes. Med Sci Sports Exerc 19:451-455

Rechtshaffen A, Kales A (1968) A manual of standardised termi- nology, techniques and scoring system for sleep stages of hu- man subjects. Government Printing Office, Washington, D.C.

Rossier J, Chapouthier G (1982) Enkephalines et endorphines. La Recherche 13:1296-1306

Schwarz L, Kindermann W (1990) fl-endorphin, adrenocortico- tropic hormone, cortisol and catecholamines during aerobic and anaerobic exercise. Eur J Appl Physiol 61:165-171

Strassman RJ, Appenzeller O, Lewy AJ, Quails CR, Peake GT (1989) Increase in plasma melatonin, fl-endorphin, and corti- sol after a 28.5 mile mountain race: relationships to perform- ance and lack of effect of Naltrexone. J Clin Endocrinol Me- tab 69: 540-545

Taub JM, Berger RJ (1976) The effects of changing the phase and duration of sleep. J Exp Psychol [Hum Percept] 2:30-41