A 2-part randomized, three-period cross-over, placebo controlled, proof of mechanism study to investigate the effect of RO5285119 on vasopressin (AVP) pathway activation in healthy male subjects

1. Right-handed (Righthandedness as confirmed on the Edinburgh Handedness inventory), healthy non smoking male adults (18 - 45 years of age)
2. BMI between 18 to 32 kg/m2 (inclusive), total weight in the range of 50-100 kg.
3. Subjects and their partners of childbearing potential must use 2 methods of contraception, one of which must be a barrier method for the duration of the study and for 90 days after the last dose.
4. Able to participate and willing to give written informed consent and to comply with the study restrictions.
5. In the investigator*s opinion, the subject is deemed appropriate for participation in the study, capable of following the study schedule of assessments and complying with the study restrictions and discontinuation of prohibited medication will not pose undue risks to the
subject.
6. Minimally completed secondary education or equivalent

1. No alcohol and substance abuse/dependance
2. History of relapsing or current psychiatric or neurological disorders, including epilepsy and migraine.
3. Subjects who, in the Investigator's judgment, pose a suicidal risk, or any subject with a history of suicidal attempts or behavior
4. Positive results for serology test for HIV, Hepatitis B, hepatitis C viruses
5. Systolic blood pressure (SBP) greater than 140 or less than 90 mm Hg, and diastolic blood pressure (DBP) greater than 90 or less than 50 mm Hg.
6. Pulse below 40 BMP or above 90 BPM
7. Clinically significant abnormality on electrocardiogram (ECG), including QTcF > 450 ms.
8. Clinically significant abnormality in parameters of clinical chemistry and urinalysis.
9. Active stomach ulcer disease or active GI bleeding.
10. Personal or family history (first or second degree relatives) of cerebral aneurysm.
11. Personal history of stroke or traumatic head injury.
12. Clinically significant abnormality in parameters of hematology or coagulation.
13. History of coagulopathies, bleeding disorders or blood dyscrasias.
14. History of hematological malignancy or myelosuppression (including iatrogenic).
15. Contraindications to have MRI scans (e.g. no metallic implants)
16. Use of prohibited medications within 2 weeks prior to randomization, or 5 half-lives (whichever is longer).
17. No participation in other trials within 90 days prior to enrollment or prior participation in part
A of study BP29412.
18. Donation or loss of blood over 500mL within three months prior to randomization
19. Chronic rhinitis, allergic rhinitis, nasal polyps or any other nasal pathology that may affect the absorption of intranasal AVP.
20. Concomitant disease, condition or treatment which might interfere with the
conduct of the study, or what would, in the opinion of the investigator,
pose an unacceptable risk to the subject in this study such as asthma or
ischemic events like Raynaud syndrome, angina pectoris or stroke.
21. unwilling to comply with lifestyles
22. Known allergic reaction to vasopressin or excipients present in the
formulation used in this study.
23. For Part B only: Contraindications for lumbar puncture:
- Any history of raised intra-cerebral pressure or clinically significant vertebral joint pathology.
- Clinically significant abnormalities in lumbar spine.
- Any major illness within one month prior to the screening examination, or febrile illness or any
- clinically significant infections within 21 days prior to CSF sampling.
- Thrombocytopenia or other bleeding diathesis (including ongoing anticoagulant therapy).
- Allergy to lidocaine.
- Any other spine abnormality that will not allow a lumbar puncture or other pathology that according
to the investigator*s judgment may interfere with the LP or may pose unacceptable risk for LP.