SIMULTANEOUS AND SERIAL INTRACEREBROVENTRICULAR ADMINISTRATION OF MDP AND URIDINE: DIFFERENTIAL EFFECTS ON NOCTURNAL SLEEP IN RATS.
MAYUMI KIMURA* and SHOJIRO INOUE Inst. Med. Dent. Eng., Tokyo Med. Dent. Univ., Kanda-Surugadai 2-3-10, Chiyoda-ku, Tokyo 101, Japan.
A compound-dependent sleep-promoting activity is demonstrated by our nocturnal 10-h intracerebroventricular (i.c.v.) infusion of muramyl dipeptide (MDP, 2.0 nmol) and uridine (10 pmol) in freely behaving rats. MDP activity is characterized by slowly enhancing slow wave sleep (SWS), whereas uridine activity is characterized by inducing a slight but continued elevation of both SWS and paradoxical sleep (PS). Since multiple factors may participate in the regulation of sleep, it is likely that MDP and uridine co-exist and interact in the brain. Hence, the interaction between the two substances, if any, was investigated by the following three kinds of experiments: (I) Simultaneous administration: Both MDP (2.0 nmol) and uridine (10 pmol) were i.c.v, infused for a 10h period (19:00-05:00). The combined infusion caused a rapid and profound increase in both SWS and PS, which lasted from the early to the middle infusion period. The time-course pattern of the sleep modulation neither accorded with that of MDP alone nor that of uridine alone. (2) Serial administration A: Uridine (5 pmol) was infused for the first 5h period (19:00-24:00). Then, MDP (1.0 nmol) was infused for the second 5h period (24:00-05:00). This serial infusion resulted in an increase in both SWS and PS which gradually appeared during the uridine-infusion period, and lasted for a few hours even after the termination of the MDP-infusion. Thus, the pretreatment of uridine provoked a prolonged sleep enhancement, augmenting the SWS-promoting effect of MDP. (3) Serial administration B: The sequence of infusion of MDP and uridine was reversed. The result was quite different from the preceding experiment; an excess SWS was observed only during the MDP-infusion period but not during the uridine-infusion period. The pre-existence of MDP seemed to interfere with the sleep-enhancing action of uridine. Thus, the two sleep substances in the combined and sequential administrations resulted in combination-dependent and sequence- dependent changes in sleep-modulatory activity. In conclusion, an interaction between the sleep factors may occur in the cerebral process of sleep regulations.
ENTRAINMENT OF SLEEP, AMBULATION AND DRINKING RHYTHMS TO VARIOUS LIGHT-INTENSITY CYCLES OF 24H PERIOD IN RATS
SETSUO USUI* and YASURO TAKAHASHI Department of Psychology, Tokyo Metropolitan Institute for Neurosciences, Fuchu, Tokyo 183, Japan
In the studies of circadian rhythms, little attention has been focused on the waveform of the environmental light-dark (LD) cycle. The present study was designed to examine the effects of 5 kinds of fluctuating light intensity cycles. Sleep, ambulation and drinking were continuously monitored in 5 min intervals in 5 male SD rats. The waveforms of the computer controlled light intensity cycles were as follows: (1)rectangular wave (RA), which was the alternation of the 12h L-period (300 ix) and the 12h D-period (0 ix); (2)sinusoidal wave (SO) with the maximum illuminance of 300 ix and the minimum of 0 ix; (3)triangular wave (TA) with the same maximum and minimum as those of SO; (4)descending saw-tooth wave (ST-d), in which illuminance was rectilinearly decreased from 300 ix to 0 ix in 24 hours and then immediately returned to 300 ix; (5)ascending saw-tooth wave (ST-a), which was the mirror image of the ST-d. Each light intensity cycle was 24h in length, 3600 ix h/day in accumulated illuminance and was maintained for 28 days. Chi-square periodograms revealed that the circadian rhythms of sleep, ambulation and drinking clearly entrained to RA, SO, TA and ST-a, but not to ST-d. During RA, about 70~ of daily sleep occurred during the L-period, and the 24h-distribution of hourly sleep amounts showed almost a square-wave shape. In contrast, during SO, TA and ST-a, the hourly sleep amounts distributed bimedally in a day with one peak in the brighter parts of the light intensity cycle and another small peak near the time of minimum illuminance. Ambulatory and drinking behaviors tended to occur during the dimmer parts of the light intensity cycles, but the waveshapes of their rhythms varied so considerably among rats that it was difficult to describe a common feature. To examine the changes in circadian rhythmic parameters, COSINOR analyses were performed. The mesor of the sleep rhythm, which represents mean daily amounts, was unchanged with all the lighting schedules, whereas those of the ambulation and drinking rhythms reduced significantly during ST-d. Amplitudes of the rhythms reduced in the order of RA, SO, TA, ST-a, ST-d for sleep and ambulation, and in the order of RA, ST-a, SO, TA, ST-d for drinking. The acrophase of the rhythms was delayed during SO and advanced significantly during ST-a in comparison with those during RA. The results indicate that the waveform of the LD cycle exerts various influences on the entrainment and waveshapes of behavioral rhythms.