Ritanserin antagonism of m-chlorophenylpiperazine effects in neuroleptic-free schizophrenics patients: Support for serotonin-2 receptor modulation of schizophrenia symptoms

Rationale: Serotonin-2 (5-HT2) receptor an- tagonism has been hypothesized to have antipsychotic activity. However, there has been limited evidence directly linking 5-HT₂ receptor antagonism to symptom control in schizophrenic patients. Objectives: In order to test this hypothesis this study evaluated the capacity of pretreatment with thereceptor antagonist 5-HT₂ ritanserin to attenuate the effects of the 5-HT agonist, m-chlorophenylpiperazine (mCPP). Methods: Twenty-two male inpatients who met DSM-III-R criteria for schizophrenia or schizoaffective disorder completed 4 test days during which 10 mg ritanserin or matched placebo was administered orally 50 min prior to the intravenous infusion of 0.1 mg/kg mCPP or saline. The test days were conducted in a randomized order under double-blind conditions. Results: mCPP mildly and transiently increased positive symptoms and behavioral activation but not negative symptoms, as assessed by the Brief Psychiatric Rating Scale. mCPP also raised plasma prolactin and cortisol levels. All of these effects were attenuated by ritanserin pretreatment. Conclusions: These data support a contribution of 5-HT₂ receptor stimulation to symptom exacerbation in schizophrenic patients and a role for 5-HT₂ receptor antagonism in the prevention of this effect.