Serotonin and the Mammalian Circadian System: II. Phase-Shifting Rat Behavioral Rhythms with Serotonergic Agonists

Journal of Biological Rhythms - Tập 8 Số 1 - Trang 17-31 - 1993
Dale M. Edgar1, Joseph D. Miller2, Rebecca A. Prosser3, Robin R. Dean4, William C. Dement4
1Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California 97304.
2Sleep Research Center, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Department of Biological Sciences, Stanford University, Stanford, California 94305
3Department of Biological Sciences, Stanford University, Stanford, California#N# 94305
4Sleep Research Center, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine

Tóm tắt

The suprachiasmatic nuclei (SCN) receive primary afferents from the median and dorsal raphe, but the role of these projections in circadian timekeeping is poorly understood. Studies of the SCN in vitro suggest that quipazine, a general serotonin (5-HT) receptor agonist, can produce circadian time-dependent phase advances and phase delays in circadian rhythms of neuronal activity. The present study addresses whether quipazine and the selective 5-HT 1A receptor agonist 8-OH-DPAT are similarly effective in vivo. Drinking and wheel-running patterns of male Wistar rats individually housed in constant darkness were monitored before and after subcutaneous administration of quipazine (5-10 mg/kg) at either circadian time (CT) 6 or CT 18, with and without running wheels available. Dose-dependent phase advances (20-180 min) were produced at CT 6. Significant phase shifts were not observed at CT 18. CT 6 quipazine-treated animals also showed a sustained and significant shortening of rhythm period (τ) following treatment (-0.28 hr; p < 0.002). τ shortening was inconsistently observed in CT 18 quipazine-treated rats. Neither quipazine-induced phase shifts nor τ effects were dependent on wheel-running activity per se. 8-OH-DPAT delivered via intracerebral ventricular treatment into the third ventricle (5 μl at 100 μM in saline) produced slightly smaller phase advances (20-90 min) at CT 6, but did not produce phase delays at CT 18 or changes in τ. These findings support in vitro evidence that 5-HT-ergic agonists can phase-shift the circadian pacemaker.

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Journal of Biological Rhythms

Tập 8 Số 1

17-31

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