Hypersensitivity of 5-HT2 receptors in OCD patients. An increased prolactin response after a challenge with meta-chlorophenylpiperazine and pre-treatment with ritanserin and placebo.
BACKGROUND
Several studies in obsessive compulsive disorder (OCD) have provided circumstantial evidence that the 5-HT-system is involved in the pathophysiology of OCD. To further examine the role of 5-HT receptors we studied the behavioural and neuroendocrine effects of different doses of meta-chlorophenylpiperazine (mCPP) in OCD patients and healthy controls, after pre-treatment with ritanserin, a 5-HT2 receptor antagonist, and placebo.


METHODS
Twenty patients and 20 healthy controls received 0.1, 0.3 or 0.5 mg/kg mCPP or placebo orally. Each subject was tested two times, receiving both times the same dosage of mCPP or placebo with ritanserin or placebo pre-treatment. All was done under double-blind conditions. OC-symptoms and hormone levels were measured.


RESULTS
The increase in prolactin level after mCPP administration was more robust in patients than in controls. The prolactin response following 0.5 mg/kg of mCPP was partially blocked by ritanserin in patients, but totally blocked in healthy controls. The cortisol responses in both groups did not differ statistically significant from each other and were entirely blocked by ritanserin. None of the subjects experienced an exacerbation of obsessive compulsive symptoms.


CONCLUSIONS
The neuroendocrine results show an enhanced susceptibility of OCD patients for the mCPP-induced prolactin response, which effect seems to be due to an increased sensitivity of 5-HT2 receptors.
de Leeuw
Aart S
AS
Meerkanten GGZ, Marina de Wolfcenter, Department of Anxiety Disorders, Ermelo, The Netherlands. aleeuw@meerkanten.nl
Westenberg
Herman G M
HG
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology*; D010879:Piperazines; D011292:Premedication; D011388:Prolactin / Q000097:blood*; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects / Q000502:physiology*; D016713:Ritanserin / Q000008:administration & dosage*; D012702:Serotonin Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
D010879:Piperazines; D044405:Receptor, Serotonin, 5-HT2C; D012702:Serotonin Antagonists; D016713:Ritanserin; D011388:Prolactin; C015068:1-(3-chlorophenyl)piperazine; D006854:Hydrocortisone