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.