Regulation of central dopamine-2 receptor sensitivity by a proportional control thermostat in humans.
Central dopamine-2 (D2) receptors are importantly involved in the pathogenesis and treatment of schizophrenia. Central D2 receptors are also involved in thermoregulation. Recently, a type of central nervous system proportional control thermostat was described that governs the magnitude of several serotonin receptor-mediated core body thermoregulatory responses in proportion to both the amount of nocturnal melatonin secreted and the minimum level of nocturnal core body temperature (Tmin). The present study investigated whether the magnitude of D2 receptor-mediated hypothermia--a putative index of central D2 receptor sensitivity--is also regulated by this proportional control thermostat in humans. Twenty healthy subjects had their 02:00 h melatonin concentrations (MT2am) and Tmin measured during consecutive sleep episodes and their core body temperature responses (TAUC) measured the next two mornings after oral ingestion of either the D2 receptor agonist bromocriptine 3.125 mg or placebo. We found that the bromocriptine-induced TAUC was significantly and independently correlated with both Tmin and MT2am. In conclusion, D2 receptor-mediated hypothermia, an index of central D2 receptor sensitivity, is regulated by a proportional control thermostat in humans. The abnormal D2 receptor function in schizophrenia could be related to dysfunction of this thermostat.
Schwartz
Paul J
PJ
Department of Psychiatry, Wright State University School of Medicine and University of Cincinnati College of Medicine, Dayton VA Medical Center, Building 302, Second Floor, 4100 West Third Street, Dayton, OH 45428, USA. Paul.Schwartz3@med.va.gov
Erk
Stanley D
SD
D000293:Adolescent; D000328:Adult; D001831:Body Temperature / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects*; D001971:Bromocriptine / Q000009:adverse effects* / Q000627:therapeutic use; D002940:Circadian Rhythm / Q000187:drug effects; D003342:Corpus Striatum / Q000378:metabolism*; D018491:Dopamine Agonists / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007035:Hypothermia / Q000139:chemically induced; D008297:Male; D008550:Melatonin / Q000097:blood; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*
D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D008550:Melatonin