Decreased serotonin2C receptor responses in male patients with schizophrenia

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-HT2C receptor agonist, was diminished in a small sample of patients with schizophrenia (SCH), suggesting decreased 5-HT2C 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-HT2C receptor responsiveness in SCH patients compared to CON and are consistent with reported association of HTR2C polymorphisms, leading to decreased expression or function of the HTR2C in patients with SCH.