The effect of the 5-HT3 receptor antagonist, alosetron, on brain responses to visceral stimulation in irritable bowel syndrome patients.
OBJECTIVE
To conduct a placebo-controlled functional brain imaging study to assess the effect of the 5-hydroxytryptamine-3 receptor antagonist, alosetron, on irritable bowel syndrome symptoms, regional brain activation by rectosigmoid distension and associated perceptual and emotional responses.


METHODS
Fifty-two non-constipated irritable bowel syndrome patients (28 female) were enrolled in a randomized, placebo-controlled trial with alosetron (1-4 mg b.d.). Thirty-seven patients completed both brain scans following randomization. Rectosigmoid stimulation was performed with a computer-controlled barostat. Changes in regional cerebral blood flow were assessed using H215O positron emission tomography. Stimulus ratings and changes in gastrointestinal symptoms were assessed using verbal descriptor scales.


RESULTS
Alosetron, but not placebo, treatment was associated with a decrease in symptom ratings, and reductions in emotional stimulus ratings. Compared to baseline, alosetron treatment was associated with reduced regional cerebral blood flow in bilateral frontotemporal and various limbic structures, including the amygdala. Compared to placebo, decreases in activity of the amygdala, ventral striatum, hypothalamus and infragenual cingulate gyrus were significantly greater after alosetron.


CONCLUSIONS
In non-constipated irritable bowel syndrome patients, 3 weeks of treatment with a 5-hydroxytryptamine-3 receptor antagonist decreases brain activity in response to unanticipated, anticipated and delivered aversive rectal stimuli in structures of the emotional motor system, and this is associated with a decrease in gastrointestinal symptoms.
Mayer
E A
EA
CURE Digestive Diseases Research Center / Neuroenteric Disease Program, Department of Medicine, University of California School of Medicine, Los Angeles, CA 90073, USA. emayer@ucla.edu
Berman
S
S
Derbyshire
S W G
SW
Suyenobu
B
B
Chang
L
L
Fitzgerald
L
L
Mandelkern
M
M
Hamm
L
L
Vogt
B
B
Naliboff
B D
BD
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D001923:Brain Chemistry; D002243:Carbolines / Q000494:pharmacology* / Q000627:therapeutic use; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003109:Colonic Diseases, Functional / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology*; D004311:Double-Blind Method; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009619:Nociceptors / Q000187:drug effects / Q000503:physiopathology; D010812:Physical Stimulation / Q000379:methods; D011985:Receptors, Serotonin / Q000032:analysis / Q000187:drug effects; D044406:Receptors, Serotonin, 5-HT3; D012007:Rectum / Q000503:physiopathology; D012702:Serotonin Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome
D002243:Carbolines; D005765:Gastrointestinal Agents; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; C090840:alosetron