Acute intravenous administration of ondansetron and m-CPP, alone and in combination, in patients with obsessive-compulsive disorder (OCD): behavioral and biological results.
Obsessive-compulsive disorder (OCD) has been linked to abnormal function of brain serotonin (5-HT) pathways. Since ondansetron is a highly selective 5-HT3 receptor antagonist, the present study was undertaken to investigate 5-HT3 function in OCD. We administered m-CPP (0.08 mg/kg i.v.) and the potent 5-HT3 antagonist, ondansetron (0.15 mg/kg i.v.), to 11 OCD patients. All of the subjects received four separate challenges (m-CPP + placebo, m-CPP + ondansetron, ondansetron + placebo and placebo + placebo). In comparison to placebo, administration of m-CPP was associated with significant behavioral effects, particularly self-rated measures of anxiety, altered self-reality, functional deficit and OCD symptoms. Pretreatment with ondansetron did not affect any of the self-rated behavioral symptoms. After administration of m-CPP relative to placebo, significant increases in plasma cortisol and prolactin were found. These changes were not affected by ondansetron. In conclusion, our results do not support the hypotheses that 5-HT3 receptor-mediated mechanisms modulate m-CPP's behavioral and neuroendocrine effects in patients with OCD.
Broocks
A
A
Section on Clinical Neuropharmacology, Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD, USA.
Pigott
T A
TA
Hill
J L
JL
Canter
S
S
Grady
T A
TA
L'Heureux
F
F
Murphy
D L
DL
D000328:Adult; D000704:Analysis of Variance; D001526:Behavioral Symptoms / Q000139:chemically induced; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009490:Neurosecretory Systems / Q000187:drug effects; D009771:Obsessive-Compulsive Disorder / Q000378:metabolism / Q000503:physiopathology*; D017294:Ondansetron / Q000008:administration & dosage; D010879:Piperazines / Q000008:administration & dosage; D011569:Psychiatric Status Rating Scales; D011985:Receptors, Serotonin / Q000145:classification / Q000502:physiology*; D012702:Serotonin Antagonists / Q000008:administration & dosage; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage; D013997:Time Factors
D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017294:Ondansetron; C015068:1-(3-chlorophenyl)piperazine