Submitted on February 3, 2005
Accepted on June 17, 2005
Antagonism of corticotropin-releasing hormone alters serotonergic-induced changes in brain temperature, but not sleep of rats
Luca Imeri1, Susanna Bianchi2, and Mark R Opp3*
1 Institute of Human Physiology II, University of Milan Medical School, Milan, Italy; Giuseppe Moruzzi Centre for Experimental Sleep Research, University of Milan Medical School, Milan, Italy; Anesthesiology, University of Michigan, Ann Arbor, MI, USA
2 Institute of Human Physiology II, University of Milan Medical School, Milan, Italy; Giuseppe Moruzzi Centre for Experimental Sleep Research, University of Milan Medical School, Milan, Italy
3 Anesthesiology, University of Michigan, Ann Arbor, MI, USA; Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, USA; Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA
* To whom correspondence should be addressed. E-mail: mopp{at}umich.edu.
Serotonin (5-hydroxytryptamine; 5-HT) 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 light:dark cycle initially increases wakefulness. Higher doses (75, 100 mg/kg) increase non-rapid 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 (HPA) 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.
