The Effect of Serotonergic Modulation on Intestinal Permeability and Visceral Hypersensitivity in Healthy Individuals and Irritable Bowel Syndrome (IBS) Patients

Inclusion Criteria:

• IBS-patients Inclusion criteria:

1. IBS will be diagnosed according to the Rome III criteria* [35]: Recurrent abdominal pain or discomfort at least 3 days per month in the last 3 monthsassociated with 2 or more of the following:

• Improvement with defecation

• Onset associated with a change in frequency of stool

• Onset associated with a change in form (appearance) of stool

• Criteria fulfilled for the last 3 months with symptom onset at least 6months prior to diagnosis

• Discomfort means an uncomfortable sensation not described as pain. Inpathophysiological research and clinical trails, a pain/discomfort frequencyof at least 2 days a week during screening evaluation is an indication forsubject's eligibility.

2. Based on the medical history and previous examination, no other causes for theabdominal complaints can be defined.

3. Age between 18 and 65 years Healthy individuals Inclusion criteria: All subjects will be screened with a standardized psychiatric examination using the miniinternational neuropsychiatric interview (MINI) to determine present psychiatric state.General psychological state will be assessed using the 17 item Hamilton depression ratingscale (HAM-D17), the Dutch version of the symptom checklist (SCL-90) and the hospitalanxiety and depression rating scale (HADS). The psychiatric evaluation will be carried outby a psychiatrist. Volunteers with deviating scores on any topic will be excluded fromparticipation. Healthy individuals between age 18 and 65 years will be included in the study.

Exclusion Criteria:

• Exclusion criteria for IBS patients:

1. Severe co-morbidity hindering a rectal barostat procedure, according to thegastroenterologist's perception.

2. Abdominal surgery, except for uncomplicated appendectomy, laparoscopiccholecystectomy or hysterectomy.

3. Inability to stop medication that can influence gastrointestinal motility orperception (like loperamide, butylscopolamine, psylliumsead (metamucil),duspatal, metoclopramide, domperidon, erytromycine), or serotonin metabolism (carbidopa) for at least 3 days before tests.

4. History of psychiatric disorders including use of psychoactive medication orpsychological symptomatology, defined as a diagnosis on the MINI, HAM-D17 scoreabove 18, global severity index score on SCL-90 for females ≥150, for males ≥131,or HADS scores ≥ 8. First-degree family members with psychiatric disorders

5. Administration of investigational drugs in the 180 days prior to the study

6. Premenstrual syndrome, dieting, pregnancy, lactation

7. Excessive alcohol consumption (>20 alcoholic consumption per week)

8. Smoking

9. Blood donation within 3 months before the study period

10. Self-admitted HIV-positive state

11. Irregular day-night rhythm Exclusion criteria for healthy individuals:

12. History of gastrointestinal, psychiatric disorders including use of psychoactivemedication or psychological symptomatology, defined as a diagnosis on the MINI,HAM-D17 score above 18, global severity index score on SCL-90 for females ≥150, formales ≥131, or HADS scores ≥ 8 First-degree family members with psychiatric disorders

13. Use of medication, except oral contraceptives, within 14 days prior to testing

14. Administration of investigational drugs in the 180 days prior to the study

15. Previous abdominal surgery (other than uncomplicated appendectomy, laparoscopiccholecystectomy and hysterectomy)

16. Premenstrual syndrome, dieting, pregnancy, lactation

17. Excessive alcohol consumption (>20 alcoholic consumption per week)

18. Smoking

19. Blood donation within 3 months before the study period

20. Self-admitted HIV-positive state

21. Irregular day-night rhythm

22. Severe co-morbidity hindering a rectal barostat procedure, according to thegastroenterologist's perception.