- Email: [email protected]
Effect of phentolamine on wakefulness and sleep during recovery from REM sleep deprivation in cats
Physiology & Behavior, Vol. 39, pp. 551-553. Copyright©PergamonJournals Ltd., 1987. Printedin the U.S.A.
0031-9384/87$3.00 + .00
BRIEF COMMUNICATION
Effect of Phentolamine on Wakefulness and Sleep During Recovery From REM Sleep Deprivation in Cats ANTERO LEPPAVUORI a AND ILKKA HILAKIVI 2
D e p a r t m e n t o f Physiology, University o f Helsinki, Siltavuorenpenger 20, SF-O0170 Helsinki, Finland R e c e i v e d 14 O c t o b e r 1986 LEPPAVUORI, A. AND I. HILAKIVI. Effect of phentolamine on wakefulness and sleep during recoveryfrom REM sleep deprivation in cats. PHYSIOL BEHAV 39(4) 551-553, 1987.--Adult cats with permanent EEG, EMG, EOG, and PGO electrodes were recorded for 24 hours started at the end of a 72-hour REMS deprivation induced by a platform-watertank procedure and after receiving IP injections of phentolamine (20 mg/kg) or saline. Exposure of the cats to the platformREMS deprivation procedure increased the percentage of REMS during the subsequent 24 hours. Phentolamine interacted with the platform REMS deprivation causing the peak of REMS percentage to occur during recovery hours 5-12. These findings indicate that blockade of alpha-receptors has an additive effect on platform-REMS deprivation induced REMS rebound in cats. REM sleep deprivation
Phentolamine
REM sleep rebound
SYSTEMIC [4,9] or intracerebral [6] injections of phentolamine, an alpha adrenoceptor antagonist, enhances the amount of rapid eye movement sleep (REMS) in cats. An increase in the amount of REMS after an initial, short-lasting reduction was also observed in rats after systemic injection of it [5]. Phentolamine was shown to increase REMS even in cats which were pretreated with a small dose of alphamethyl-paratyrosine, an inhibitor of noradrenaline synthesis [3]. Based on this finding it was previously suggested that the efficacy of phentolamine to increase REMS is due to the hypersensitivity of the cerebral noradrenergic systems to alpha blockade especially when the turnover of noradrenaline is low [3,4]. The turnover of noradrenaline in the brain is proposed to be increased during and after REMS deprivation [8]. Therefore, in this study we have tested whether phentolamine is able to increase the amount of REMS in cats during REMS rebound.
METHOD
Subjects Six male cats of the cat colony of the Department of Physiology, University of Helsinki, served as subjects. The body weights of the cats were 3.0--4.0 kg. Under general
Cat
anesthesia (pentobarbital 50 mg/kg IP) electrodes were inserted into the skull outside the dura mater for recording of electrocorticogram, into one of the lateral geniculate bodies for ponto-geniculo-occipital waves, into either one of the frontal sinuses for eye movements, and finally into the dorsal neck muscles for electromyography as described elsewhere [1, 2, 4, 9]. During three weeks following the surgical operations and during the intervals between REMS deprivation and sleep-wake recording periods the cats were kept in a group of 6--8 in a room of 8 m 2 where an ambient temperature of 20-23°C was maintained. The illumination cycle was 12 hour light-12 hour dark with lights on at 6.00 a.m.
REMS Deprivation Procedures In the REMS deprivation procedure cats are placed on circular platforms with a diameter of 12-13 cm, surrounded by water, in a stainless steel tank with the dimensions of 100× 100× 120 cm. During REMS animals lose their ability to maintain tone in striated muscles and thus their postural balance on the small platform is disturbed to such an extent that they fall into the water. Cats learn rapidly to sleep only slow wave sleep when sitting on these platforms [12]. In the present study the cats were kept on the platforms for three days
1Present address: Department of Psychiatry, Helsinki University Central Hospital, Haartmaninkatu 3, 00290 Helsinki. ~Requests for reprints should be addressed to Ilkka Hilakivi.
552
LEPP,~VUORI AND HILAKIVI
w
Lu
AW DW
LSWS
DSWS
REMS
FIG. 1. Effect of phentolamine on wakefulness and sleep in cats during six consecutive 4-hr periods of the 24-hr recovery period after a 72-hr REMS deprivation. The mean percentages of the different stages of wakefulness and sleep after IP injections of sodium chloride (rebound) or phentolamine 20 mg/kg (rebound + PHE 20 mg/kg) are shown. The respective mean percentages of recordings of the same cats without any preceding exposure are also shown (baseline). AW=active wakefulness, DW=drowsy wakefulness, LSWS=light slow wave sleep, DSWS=deep slow wave sleep, and REMS=rapid eye movement sleep.
and nights with an e x c e p t i o n of one daily hour b e t w e e n 9--10 a.m. During this time the cats were allowed to m o v e and eat freely. The average body weight of the cats did not change in the course of the R E M S deprivation. This procedure has been shown to almost abolish R E M S in cats during the exposure time [12].
TABLE 1 EFFECT OF PHENTOLAMINE ON WAKEFULNESS AND SLEEP DURING THE FIRST 24 HOURS OF RECOVERY FROM A 72-HOUR EXPOSURE TO THE PLATFORM REMS DEPRIVATION PROCEDURE IN CATS
Baseline
PlatformREMS Deprivation
PlatformREMS Deprivation + Phentolamine 20 mg/kg
16.4 ± 5.3
10.5 ± 6.8*
11.2 ± 4.9
20.1 ± 6.6
14.8 ± 6.0
17.1 ± 7.5
19.5 ± 4.4
14.8 _+ 8.3
10.6 ±
29.4 _+ 7.1
36.3 ± 8.8
30.6 ± 7.1
14.5 ± 4.0
23.5 ± 9.6*
30.5 ± 6.8*
Polygraphic Recordings The sleep-wake recordings w e r e carried out in separate chambers with the dimensions of 4 0 × 7 8 × 7 8 cm. F o o d and water were provided ad l~b. Otherwise the recording conditions were similar to the housing conditions. After the R E M S deprivation procedures recordings with a Kaiser electroencephalograph w e r e started at 3--4 p.m. Paper-speeds o f 5 mm/sec were used. In the E E G recordings the time constants o f 0.3 sec, gains o f 5 0 - 1 0 0 / z V / c m and low pass filters of 50 H z were used. E l e c t r o c o r t i c o g r a m s , e l e c t r o m y o g r a m s , eye m o v e m e n t s and electrical activities of one of the lateral geniculate bodies w e r e continuously r e c o r d e d for 24 hours on paper. The records thus obtained w e r e hand-scored in 1 min epochs as described earlier [1, 3, 4, 9] into active waking (AW), drowsy waking (DW), light slow w a v e sleep (LSWS), deep slow w a v e sleep (DSWS), and rapid e y e m o v e m e n t sleep (REMS).
Experimental Design Before e x p o s u r e to the R E M S deprivation procedures and after habituation to the sleep-wake recording chambers during two days and nights 24-hr baseline recordings were carried out. After the R E M S deprivation periods the cats r e c e i v e d either phentolamine 20 mg/kg of body weight dissolved in methanesulfonate and diluted in distilled w a t e r or a respective v o l u m e of 0.9% sodium chloride. This watersolution o f methanesulfonate does not affect sleep in cats [4]. After the injections the recordings w e r e started. T w o cats were recorded simultaneously. E a c h cat acted as its o w n control with an interval of three weeks.
Active Waking (%) Drowsy Waking (%) Light SWS (%) Deep SWS (%) REM Sleep (%) REMS Episode Duration (rain) REMS Episode Number
4.6 +_ 0.4 44.7 ± 8.7
5.4 ±
1.8
73.0 _+ 19.4"
6.5 ±
2.6
1.9
70.0 ± 17.0
Means - S.D. are given. N=6 cats in each group. Paired, twotailed Student's t-test after ANOVA: *p<0.05.
Data Analysis The hand-scored data w e r e stored on a disk m e m o r y of a K a y p r o II m i c r o c o m p u t e r (Kaypro Co., Solana Beach, CA) for data reduction. T h e n the data were transmitted to a Burroughs-computer for statistical analysis using the B M D P
P H E N T O L A M I N E AND REMS R E B O U N D
553
2V statistical software (University of California, Los Angeles). Possible differences between the three groups in the means of percentages, numbers and durations of the five stages of wakefulness and sleep during the six consecutive time intervals were tested using a 2-way analysis of variance with repeated measures on the consecutive 4-hour periods (treatment and the consecutive 4-hour periods within). In case of a statistical significance in the ANOVA, a paired 2-tailed Student's t-test was used in comparisons between two of the three groups studied.
larger after combined treatment than after the REMS deprivation only (t =2.97, p<0.05, see also Table 1). There was an interaction on the amount of REMS between platform REMS-deprivation and phentolamine plus platform-REMS deprivation treatments, F(10,40)=3.86, p<0.001. The 24-hr percentage of active wakefulness was decreased in both experimental groups as compared with the baseline, F(2,8)=38.1, t=4.71 and 3.22, p<0.001.
RESULTS
The highest percentage of REMS relative to total recording time occurred during recovery hours 5-12, which is the period when the effect of systemically administered phentolamine on REMS is at its maximum [4,9]. This high REMS percentage (40%) matches with the percentage observed after microinfusion of phentolamine into the locus coeruleus areas in the cat brain stem [6], and may thus represent a physiological, centrally regulated upper limit for the proportion of time adult cats are able to spend in REMS. The present results are at variance with those obtained in rats. In this species phentolamine (10 mg/kg) and phenoxybenzamine, another alpha-blocker, reduced the rebound of REM sleep during the 48 hours following platform REMS deprivation [10]. In another study on rats the REMS rebound was attenuated by phenoxybenzamine which was administered already during the REMS deprivation procedure [11]. Thus, the data available at present suggests a species difference between rats and cats in the effect of phentolamine on REMS, possibly due to greater vulnerability of rats to its cardiovascular effects. Furthermore, our results suggest that phentolamine increases REMS efficiently in cats even during REMS rebound when the turnover of noradrenaline is proposed to be accelerated [8].
DISCUSSION
Effect o f Platform R E M S Deprivation Procedure The REMS deprivation procedure increased the percentage of REMS during the first 16 hours of recovery time from the baseline of 14.5_+3.7% to 27.3_+9.9% (mean_+S.D., t=4.78, p<0.001). The 24-hr percentage and number of REMS episodes were increased and that of active wakefulness decreased; the duration of REMS episodes was not changed (Table 1). Effect o f Phentolamine Plus Platform REMS Deprivation Procedure As can also be seen in Fig. 1 phentolamine increased the percentage of REMS during recording hours 5-12 to 36.7_ + 14.0% from the baseline of 16.7_+6.6%, F(10,40)=3.85, p<0.001, t=5.12, p<0.001, and from the rebound group value of 26.4_+4.0% (t=2.58, p<0.05). Moreover, the cats which received phentolamine showed increased amounts of REMS for a longer period of time than the cats which were only REMS deprived prior to the recordings, F(5,20)= 10.1, t=5,42, p<0.001. Even the 24-hr percentage of REMS was
REFERENCES
1. Hilakivi, I. and A. Lepp~vuori. Effects of methoxamine, an alpha-I adrenoceptor agonist, and prazosin, an alpha-1 antagonist, on the stages of the sleep-waking cycle in the cat. Acta Physiol Scand 120: 363-372, 1984. 2. Leinonen, L. and D. Stenberg. Sleep in Macaca arctoides and the effects of prazosin. Physiol Behav 37: 199-202, 1986. 3. Lepp/ivuori, A. The effects of alpha-adrenergic agonist or antagonist on sleep during blockade of catecholamine synthesis in the cat. Brain Res 193:117-128, 1980. 4. Lepp/ivuori, A. and P. Putkonen. Alpha-adrenoceptive influences on the control of the sleep-waking cycle of the cat. Brain Res 193: 95-115, 1980. 5. Makel~i, J. P. and I. T. Hilakivi. Effect of alpha-adrenoceptor blockade on sleep and wakefulness in the rat. Pharmacol Biochem Behav 24: 613-616, 1986. 6. Masserano, J. M. and C. King. Effects on sleep of phentolamine and epinephrine infused into the locus coeruleus of cats. Eur J Pharmacol 84: 199-204, 1982. 7. Pellejero, T., J. M. Monti, J. Baglietto, H. Jantos, S. Pazos, V. Cichevski and M. Hawkins. Effects of methoxamine and a-adrenoceptor antagonists, prazosin and yohimbine, on the sleep-wake cycle of the rat. Sleep 7: 365-372, 1984.
8. Pujol, J., J. Mouret, M. Jouvet and J. Glowinski. Increased turnover of cerebral norepinephrine during rebound of paradoxical sleep in the rat. Science 159:112-114, 1968. 9. Putkonen, P. and A. Lepp/ivuori. Increase in paradoxical sleep after phentolamine, an alpha-adrenoceptor antagonist. Acta Physiol Scand 100: 488-490, 1977. 10. Radulovacki, M., M. Wojcik, C. Fornal and R. Miletich. Elimination of REM sleep rebound in rats by a-adrenoceptor blockers, phentolamine and phenoxybenzamine. Pharrnacol Biochem Behav 13: 51-55, 1980. 11. Radulovacki, M., W. Wojcik, R. Walovitch and M. Brodie. Phenoxybenzamine and bromocriptine attenuate need for REM sleep in rats. Pharmacol Biochem Behav 14: 371-375, 1980. 12. Vimont-Vicary, P., D. Jouvet-Mounier and F. Delorme. Effets EEG et comportementaux des privations de sommeil paradoxal chez le chat. Electroencephalogr Clin Neurophysiol 20: 439449, 1966.
0031-9384/87$3.00 + .00
BRIEF COMMUNICATION
Effect of Phentolamine on Wakefulness and Sleep During Recovery From REM Sleep Deprivation in Cats ANTERO LEPPAVUORI a AND ILKKA HILAKIVI 2
D e p a r t m e n t o f Physiology, University o f Helsinki, Siltavuorenpenger 20, SF-O0170 Helsinki, Finland R e c e i v e d 14 O c t o b e r 1986 LEPPAVUORI, A. AND I. HILAKIVI. Effect of phentolamine on wakefulness and sleep during recoveryfrom REM sleep deprivation in cats. PHYSIOL BEHAV 39(4) 551-553, 1987.--Adult cats with permanent EEG, EMG, EOG, and PGO electrodes were recorded for 24 hours started at the end of a 72-hour REMS deprivation induced by a platform-watertank procedure and after receiving IP injections of phentolamine (20 mg/kg) or saline. Exposure of the cats to the platformREMS deprivation procedure increased the percentage of REMS during the subsequent 24 hours. Phentolamine interacted with the platform REMS deprivation causing the peak of REMS percentage to occur during recovery hours 5-12. These findings indicate that blockade of alpha-receptors has an additive effect on platform-REMS deprivation induced REMS rebound in cats. REM sleep deprivation
Phentolamine
REM sleep rebound
SYSTEMIC [4,9] or intracerebral [6] injections of phentolamine, an alpha adrenoceptor antagonist, enhances the amount of rapid eye movement sleep (REMS) in cats. An increase in the amount of REMS after an initial, short-lasting reduction was also observed in rats after systemic injection of it [5]. Phentolamine was shown to increase REMS even in cats which were pretreated with a small dose of alphamethyl-paratyrosine, an inhibitor of noradrenaline synthesis [3]. Based on this finding it was previously suggested that the efficacy of phentolamine to increase REMS is due to the hypersensitivity of the cerebral noradrenergic systems to alpha blockade especially when the turnover of noradrenaline is low [3,4]. The turnover of noradrenaline in the brain is proposed to be increased during and after REMS deprivation [8]. Therefore, in this study we have tested whether phentolamine is able to increase the amount of REMS in cats during REMS rebound.
METHOD
Subjects Six male cats of the cat colony of the Department of Physiology, University of Helsinki, served as subjects. The body weights of the cats were 3.0--4.0 kg. Under general
Cat
anesthesia (pentobarbital 50 mg/kg IP) electrodes were inserted into the skull outside the dura mater for recording of electrocorticogram, into one of the lateral geniculate bodies for ponto-geniculo-occipital waves, into either one of the frontal sinuses for eye movements, and finally into the dorsal neck muscles for electromyography as described elsewhere [1, 2, 4, 9]. During three weeks following the surgical operations and during the intervals between REMS deprivation and sleep-wake recording periods the cats were kept in a group of 6--8 in a room of 8 m 2 where an ambient temperature of 20-23°C was maintained. The illumination cycle was 12 hour light-12 hour dark with lights on at 6.00 a.m.
REMS Deprivation Procedures In the REMS deprivation procedure cats are placed on circular platforms with a diameter of 12-13 cm, surrounded by water, in a stainless steel tank with the dimensions of 100× 100× 120 cm. During REMS animals lose their ability to maintain tone in striated muscles and thus their postural balance on the small platform is disturbed to such an extent that they fall into the water. Cats learn rapidly to sleep only slow wave sleep when sitting on these platforms [12]. In the present study the cats were kept on the platforms for three days
1Present address: Department of Psychiatry, Helsinki University Central Hospital, Haartmaninkatu 3, 00290 Helsinki. ~Requests for reprints should be addressed to Ilkka Hilakivi.
552
LEPP,~VUORI AND HILAKIVI
w
Lu
AW DW
LSWS
DSWS
REMS
FIG. 1. Effect of phentolamine on wakefulness and sleep in cats during six consecutive 4-hr periods of the 24-hr recovery period after a 72-hr REMS deprivation. The mean percentages of the different stages of wakefulness and sleep after IP injections of sodium chloride (rebound) or phentolamine 20 mg/kg (rebound + PHE 20 mg/kg) are shown. The respective mean percentages of recordings of the same cats without any preceding exposure are also shown (baseline). AW=active wakefulness, DW=drowsy wakefulness, LSWS=light slow wave sleep, DSWS=deep slow wave sleep, and REMS=rapid eye movement sleep.
and nights with an e x c e p t i o n of one daily hour b e t w e e n 9--10 a.m. During this time the cats were allowed to m o v e and eat freely. The average body weight of the cats did not change in the course of the R E M S deprivation. This procedure has been shown to almost abolish R E M S in cats during the exposure time [12].
TABLE 1 EFFECT OF PHENTOLAMINE ON WAKEFULNESS AND SLEEP DURING THE FIRST 24 HOURS OF RECOVERY FROM A 72-HOUR EXPOSURE TO THE PLATFORM REMS DEPRIVATION PROCEDURE IN CATS
Baseline
PlatformREMS Deprivation
PlatformREMS Deprivation + Phentolamine 20 mg/kg
16.4 ± 5.3
10.5 ± 6.8*
11.2 ± 4.9
20.1 ± 6.6
14.8 ± 6.0
17.1 ± 7.5
19.5 ± 4.4
14.8 _+ 8.3
10.6 ±
29.4 _+ 7.1
36.3 ± 8.8
30.6 ± 7.1
14.5 ± 4.0
23.5 ± 9.6*
30.5 ± 6.8*
Polygraphic Recordings The sleep-wake recordings w e r e carried out in separate chambers with the dimensions of 4 0 × 7 8 × 7 8 cm. F o o d and water were provided ad l~b. Otherwise the recording conditions were similar to the housing conditions. After the R E M S deprivation procedures recordings with a Kaiser electroencephalograph w e r e started at 3--4 p.m. Paper-speeds o f 5 mm/sec were used. In the E E G recordings the time constants o f 0.3 sec, gains o f 5 0 - 1 0 0 / z V / c m and low pass filters of 50 H z were used. E l e c t r o c o r t i c o g r a m s , e l e c t r o m y o g r a m s , eye m o v e m e n t s and electrical activities of one of the lateral geniculate bodies w e r e continuously r e c o r d e d for 24 hours on paper. The records thus obtained w e r e hand-scored in 1 min epochs as described earlier [1, 3, 4, 9] into active waking (AW), drowsy waking (DW), light slow w a v e sleep (LSWS), deep slow w a v e sleep (DSWS), and rapid e y e m o v e m e n t sleep (REMS).
Experimental Design Before e x p o s u r e to the R E M S deprivation procedures and after habituation to the sleep-wake recording chambers during two days and nights 24-hr baseline recordings were carried out. After the R E M S deprivation periods the cats r e c e i v e d either phentolamine 20 mg/kg of body weight dissolved in methanesulfonate and diluted in distilled w a t e r or a respective v o l u m e of 0.9% sodium chloride. This watersolution o f methanesulfonate does not affect sleep in cats [4]. After the injections the recordings w e r e started. T w o cats were recorded simultaneously. E a c h cat acted as its o w n control with an interval of three weeks.
Active Waking (%) Drowsy Waking (%) Light SWS (%) Deep SWS (%) REM Sleep (%) REMS Episode Duration (rain) REMS Episode Number
4.6 +_ 0.4 44.7 ± 8.7
5.4 ±
1.8
73.0 _+ 19.4"
6.5 ±
2.6
1.9
70.0 ± 17.0
Means - S.D. are given. N=6 cats in each group. Paired, twotailed Student's t-test after ANOVA: *p<0.05.
Data Analysis The hand-scored data w e r e stored on a disk m e m o r y of a K a y p r o II m i c r o c o m p u t e r (Kaypro Co., Solana Beach, CA) for data reduction. T h e n the data were transmitted to a Burroughs-computer for statistical analysis using the B M D P
P H E N T O L A M I N E AND REMS R E B O U N D
553
2V statistical software (University of California, Los Angeles). Possible differences between the three groups in the means of percentages, numbers and durations of the five stages of wakefulness and sleep during the six consecutive time intervals were tested using a 2-way analysis of variance with repeated measures on the consecutive 4-hour periods (treatment and the consecutive 4-hour periods within). In case of a statistical significance in the ANOVA, a paired 2-tailed Student's t-test was used in comparisons between two of the three groups studied.
larger after combined treatment than after the REMS deprivation only (t =2.97, p<0.05, see also Table 1). There was an interaction on the amount of REMS between platform REMS-deprivation and phentolamine plus platform-REMS deprivation treatments, F(10,40)=3.86, p<0.001. The 24-hr percentage of active wakefulness was decreased in both experimental groups as compared with the baseline, F(2,8)=38.1, t=4.71 and 3.22, p<0.001.
RESULTS
The highest percentage of REMS relative to total recording time occurred during recovery hours 5-12, which is the period when the effect of systemically administered phentolamine on REMS is at its maximum [4,9]. This high REMS percentage (40%) matches with the percentage observed after microinfusion of phentolamine into the locus coeruleus areas in the cat brain stem [6], and may thus represent a physiological, centrally regulated upper limit for the proportion of time adult cats are able to spend in REMS. The present results are at variance with those obtained in rats. In this species phentolamine (10 mg/kg) and phenoxybenzamine, another alpha-blocker, reduced the rebound of REM sleep during the 48 hours following platform REMS deprivation [10]. In another study on rats the REMS rebound was attenuated by phenoxybenzamine which was administered already during the REMS deprivation procedure [11]. Thus, the data available at present suggests a species difference between rats and cats in the effect of phentolamine on REMS, possibly due to greater vulnerability of rats to its cardiovascular effects. Furthermore, our results suggest that phentolamine increases REMS efficiently in cats even during REMS rebound when the turnover of noradrenaline is proposed to be accelerated [8].
DISCUSSION
Effect o f Platform R E M S Deprivation Procedure The REMS deprivation procedure increased the percentage of REMS during the first 16 hours of recovery time from the baseline of 14.5_+3.7% to 27.3_+9.9% (mean_+S.D., t=4.78, p<0.001). The 24-hr percentage and number of REMS episodes were increased and that of active wakefulness decreased; the duration of REMS episodes was not changed (Table 1). Effect o f Phentolamine Plus Platform REMS Deprivation Procedure As can also be seen in Fig. 1 phentolamine increased the percentage of REMS during recording hours 5-12 to 36.7_ + 14.0% from the baseline of 16.7_+6.6%, F(10,40)=3.85, p<0.001, t=5.12, p<0.001, and from the rebound group value of 26.4_+4.0% (t=2.58, p<0.05). Moreover, the cats which received phentolamine showed increased amounts of REMS for a longer period of time than the cats which were only REMS deprived prior to the recordings, F(5,20)= 10.1, t=5,42, p<0.001. Even the 24-hr percentage of REMS was
REFERENCES
1. Hilakivi, I. and A. Lepp~vuori. Effects of methoxamine, an alpha-I adrenoceptor agonist, and prazosin, an alpha-1 antagonist, on the stages of the sleep-waking cycle in the cat. Acta Physiol Scand 120: 363-372, 1984. 2. Leinonen, L. and D. Stenberg. Sleep in Macaca arctoides and the effects of prazosin. Physiol Behav 37: 199-202, 1986. 3. Lepp/ivuori, A. The effects of alpha-adrenergic agonist or antagonist on sleep during blockade of catecholamine synthesis in the cat. Brain Res 193:117-128, 1980. 4. Lepp/ivuori, A. and P. Putkonen. Alpha-adrenoceptive influences on the control of the sleep-waking cycle of the cat. Brain Res 193: 95-115, 1980. 5. Makel~i, J. P. and I. T. Hilakivi. Effect of alpha-adrenoceptor blockade on sleep and wakefulness in the rat. Pharmacol Biochem Behav 24: 613-616, 1986. 6. Masserano, J. M. and C. King. Effects on sleep of phentolamine and epinephrine infused into the locus coeruleus of cats. Eur J Pharmacol 84: 199-204, 1982. 7. Pellejero, T., J. M. Monti, J. Baglietto, H. Jantos, S. Pazos, V. Cichevski and M. Hawkins. Effects of methoxamine and a-adrenoceptor antagonists, prazosin and yohimbine, on the sleep-wake cycle of the rat. Sleep 7: 365-372, 1984.
8. Pujol, J., J. Mouret, M. Jouvet and J. Glowinski. Increased turnover of cerebral norepinephrine during rebound of paradoxical sleep in the rat. Science 159:112-114, 1968. 9. Putkonen, P. and A. Lepp/ivuori. Increase in paradoxical sleep after phentolamine, an alpha-adrenoceptor antagonist. Acta Physiol Scand 100: 488-490, 1977. 10. Radulovacki, M., M. Wojcik, C. Fornal and R. Miletich. Elimination of REM sleep rebound in rats by a-adrenoceptor blockers, phentolamine and phenoxybenzamine. Pharrnacol Biochem Behav 13: 51-55, 1980. 11. Radulovacki, M., W. Wojcik, R. Walovitch and M. Brodie. Phenoxybenzamine and bromocriptine attenuate need for REM sleep in rats. Pharmacol Biochem Behav 14: 371-375, 1980. 12. Vimont-Vicary, P., D. Jouvet-Mounier and F. Delorme. Effets EEG et comportementaux des privations de sommeil paradoxal chez le chat. Electroencephalogr Clin Neurophysiol 20: 439449, 1966.