Chronotypic action of theophylline and of pentobarbital as circadian zeitgebers in the rat

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Science  20 Jun 1975:
Vol. 188, Issue 4194, pp. 1212-1215
DOI: 10.1126/science.1145192


In the rat the deep body temperature rhythm, monitored by telemetry, can be reset in a predictable direction by a stimulant (theopylline) and by a depressant (pentobarbital). When the drugs are applied immediately before or during the early active phases of the circadian cycle, the rhythm is set back (phase delay). When applied later, past the thermal peak, theophylline, but not pentobarbital, shifts the rhythm ahead (phase advance). Theophylline and pentobarbital in addition to having a number of already established pharmacological properties are now further identified as chronobiotics: they are drugs that may be used to alter the biological time structure by rephasing a circadian rhythm.