title: Decreased serotonin2C receptor responses in male patients with schizophrenia.
abstract: Serotonin (5-HT)2C receptors in brain affect psychosis, reward, substance abuse, anxiety, other behaviors, appetite, body temperature, and other physiological measures. They also have been implicated in antipsychotic drug efficacy and side effects. We previously reported that the hyperthermia following administration of MK-212, a predominantly 5-HT(2C) receptor agonist, was diminished in a small sample of patients with schizophrenia (SCH), suggesting decreased 5-HT(2C) receptor responsiveness. We have now studied the responses to oral MK-212 and placebo in a larger sample of unmedicated male SCH (n = 69) and normal controls (CON) (n = 33), and assessed the influence of comorbid substance abuse (SA) on oral body temperature, behavioral responses, etc. The placebo-adjusted oral body temperature response to MK-212 was significantly lower in SCH compared to CON and not significantly different between the SCH with or without SA. Some behavioral responses to MK-212, e.g. self-rated feelings of increased anxiety, depression and decreased calmness, or good overall feeling, were significantly lower in the SCH patients compared to CON. These results add to the evidence for diminished 5-HT(2C) receptor responsiveness in SCH patients compared to CON and are consistent with reported association of HTR(2C) polymorphisms, leading to decreased expression or function of the HTR(2C) in patients with SCH.
authors: Department of Psychiatry, School of Medicine, Vanderbilt University, Nashville, TN, USA; Tennessee Valley VA Healthcare System, Nashville Campus, Nashville, TN, USA.
authors: Myung Ae
authors: MA
authors: Lee
authors: Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors: Karuna
authors: K
authors: Jayathilake
authors: Department of Psychiatry, Seoul National Hospital, Seoul, South Korea.
authors: Min Young
authors: MY
authors: Sim
authors: Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address: h-meltzer@northwestern.edu.
authors: Herbert Y
authors: HY
authors: Meltzer
mesh_terms: D000328:Adult; D001833:Body Temperature Regulation / Q000187:drug effects* / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D011599:Psychopathology; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012559:Schizophrenia / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D012701:Serotonin / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D012720:Severity of Illness Index
chemical_list: D011719:Pyrazines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D012701:Serotonin; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D006854:Hydrocortisone
keywords: 5-HT(2C); Anxiety; MK-212; Schizophrenia; Serotonin; Temperature