Characterization of the Daily Oxytocin Rhythm in Primate Cerebrospinal Fluid1

The circadian characteristics of the daily rhythm in oxytocin (OT) concentrations in cerebrospinal fluid (CSF) were studied in the rhesus monkey. Monkeys subjected to constant light or constant dark for periods of 3 to 6 days manifested persistence of the CSF OT rhythm. A 12-hr phase shift in the light-dark cycle resulted in a resynchronization of the rhythm to the new lighting schedule within 3 to 4 days. Altering the daily feeding and care schedule during a period of constant darkness did not alter the expression or timing of the CSF OT rhythm significantly. These results suggest that the OT rhythm is endogenously generated and that the daily light-dark cycle normally synchronizes the rhythm to the 24-hr cycle. Recently, we reported that there is a large daily rhythm in the oxytocin (OT) concentration in cerebrospinal fluid (CSF) of male rhesus monkeys (Perlow et al., 1981). Daytime CSF OT levels are 3to 12-fold higher than night-time values. Interestingly, the CSF rhythm is not accompanied by a diurnal pattern of plasma OT concentrations. The presence of an OT rhythm confined to CSF suggests that the CSF is a vehicle for OT distribution to different parts of the brain where the peptide may have important neuromodulator functions. In the present study, we sought to determine whether the CSF OT rhythm is generated endogenously and whether the daily light-dark cycle functions to coordinate the CSF rhythm to the solar day. Materials and Methods The monkey model for these experiments has been described previously in detail (Reppert et al., 1979). Briefly, adult male rhesus monkeys weighing 5.5 to 6.5 ’ The expert technical assistance of Ms. Rubye Lawrence is appreciated. We also thank Ms. Sharon Schuler and Ms. Mary Towles for their excellent secretarial work. This work was supported by Public Health Service Grants HD-06335 and HD-14427 from the National Institute of Child Health and Human Development. S. M. R. is a Research Fellow of the Charles A. King Trust, Boston, MA. ‘To whom correspondence should be addressed at Research and Education Institute, Building A-17, 1124 West Carson Street, Torrance, CA 90502. kg were adapted to primate chairs. Each animal was kept in a separate, sound-attenuated isolation chamber; the chambers were cleaned between 10 A.M. and 12 noon. Food was placed on the feeding trays between 10 A.M. and 12 noon unless otherwise specified and remained available until the following day; this was done for experimental convenience and not as a means to restrict feeding to a particular time of day. Water was available ad Zibitum. The diurnal lighting schedule consisted of 12 hr of light per day (LD 12:12), with lights on from 6 A.M. to 6 P.M. CSF was withdrawn continuously at a rate of approximately 1 ml/hr from an indwelling polyethylene catheter terminating in the subarachnoid space at the high cervical to low cisternal region. CSF was collected in 2-hr fractions by an automated fraction collector. Samples remained at room temperature for approximately 2 hr prior to refrigeration at 4°C. Fractions were collected in the morning and frozen at -20°C until assayed. The double antibody OT radioimmunoassay (RIA) system has been described previously; 100 d of unextracted CSF were assayed in each tube (Weitzman et al., 1978). United States Pharmacopeia posterior pituitary reference material (2.4 U.S.P. posterior pituitary units of oxytocic activity/mg) was used as the standard in the RIA. All samples from a single experiment in an individual monkey were run in the same assay. Sensitivity of the RIA was defined as the amount of OT which would displace 10% of the lz51-OT in the assay tube. Samples