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This Article Full Text Full Text (PDF) All Versions of this Article: 289/4/R1116    most recent 00074.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Imeri, L. Articles by Opp, M. R. Search for Related Content PubMed PubMed Citation Articles by Imeri, L. Articles by Opp, M. R.

SLEEP AND TEMPERATURE REGULATION

Antagonism of corticotropin-releasing hormone alters serotonergic-induced changes in brain temperature, but not sleep, of rats

¹Institute of Human Physiology II, and ²Giuseppe Moruzzi Centre for Experimental Sleep Research, University of Milan Medical School, Milan, Italy; and ³Department of Anesthesiology, ⁴Neuroscience Graduate Program, and ⁵Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan

Submitted 3 February 2005 ; accepted in final form 17 June 2005

Serotonin is involved in many physiological processes, including the regulation of sleep and body temperature. Administration into rats of low doses (25, 50 mg/kg) of the 5-HT precursor L-5-hydroxytryptophan (5-HTP) at the beginning of the dark period of the 12:12-h light-dark cycle initially increases wakefulness. Higher doses (75, 100 mg/kg) increase nonrapid eye movement (NREM) sleep. The initial enhancement of wakefulness after low-dose 5-HTP administration may be a direct action of 5-HT in brain or due to 5-HT-induced activation of other arousal-promoting systems. One candidate arousal-promoting system is corticotropin-releasing hormone (CRH) and the hypothalamic-pituitary-adrenal axis. Serotonergic activation by 5-HTP at the beginning of the dark period also induces hypothermia. Because sleep and body temperature are influenced by circadian factors, one aim of this study was to determine responses to 5-HTP when administered at a different circadian time, the beginning of the light period. Results obtained show that all doses of 5-HTP (25–100 mg/kg) administered at light onset initially increase wakefulness; NREM sleep increases only after a long delay, during the subsequent dark period. Serotonergic activation by 5-HTP at light onset induces hypothermia, the time course of which is biphasic after higher doses (75, 100 mg/kg). Intracerebroventricular pretreatment with the CRH receptor antagonist -helical CRH does not alter the impact of 5-HTP on sleep-wake behavior but potentiates the hypothermic response to 50 mg/kg 5-HTP. These data suggest that serotonergic activation by peripheral administration of 5-HTP may modulate sleep-wake behavior by mechanisms in addition to direct actions in brain and that circadian systems are important determinants of the impact of serotonergic activation on sleep and body temperature.

thermoregulation; hypothermia; hypothalamic-pituitary-adrenal axis; corticotropin-releasing factor; 5-hydroxytryptamine