Serotonin 1A receptors, melatonin, and the proportional control thermostat in patients with winter depression

Author(s): Rosenthal, N. E., Wehr, T. A.

Journal/Book: Arch Gen Psychiatry. 1998; 55: 515 N State St, Chicago, IL 60610. Amer Medical Assoc. 897-903.

Abstract: Background: In patients with seasonal affective disorder, light treatment lowers core temperature during sleep in proportion to its antidepressant efficacy. The regulation of the level of core temperature during sleep is linked with a proportional control thermostat in the central nervous system whose operation appears abnormal in patients with seasonal affective disorder. Because both melatonin and serotonin 1A receptor activation also lower core temperature, we investigated the relationship between ii) endogenous melatonin and core temperature profiles, (2) the proportional control thermostat, and (3) the core hypothermic response to the serotonin 1A receptor partial agonist ipsapirone hydrochloride in patients with seasonal affective disorder and healthy controls. Methods: Eighteen patients with seasonal affective disorder and 18 controls first completed a 24-hour study in which their melatonin profiles were characterized. Subjects then returned 3 to 5 days later for the first of 2 drug challenges (ipsapirone hydrochloride, 0.3 mg/kg, or placebo), each separated by 3 to 5 days. Overnight rectal and facial temperatures were recorded before and after each drug challenge. Results: The magnitudes of the core hypothermic responses to ipsapirone were (1) not different between groups and (2) independently correlated with both the levels of the previous nights' core temperature-minima (P = .002) and the amounts of nocturnal melatonin secreted (P<.001). Conclusion: The daytime regulation of core temperature by serotonin 1A receptors appears normal in seasonal affective disorder. The magnitude of serotonin 1A receptor-activated hypothermia is governed by a central nervous system proportional control thermostat whose operation appears modulated by both melatonin and the level of the core temperature minimum.

Note: Article Rosenthal NE, NIMH, Clin Psychobiol Branch, Bldg 10, Room 3S-231, 10 Ctr Dr, MSC-1390, Bethesda,MD 20892 USA

Keyword(s): SEASONAL AFFECTIVE-DISORDER; BODY-TEMPERATURE; META-CHLOROPHENYLPIPERAZINE; HYPOTHERMIC RESPONSE; ENDOCRINE RESPONSES; RECOGNITION SITES; CORE TEMPERATURE; MAJOR DEPRESSION; INDUCED DECREASE; HUMANS

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