Use of antagonists of ghrelin or ghrelin receptor to prevent or treat stress-sensitive psychiatric illness
The invention relates to methods of protecting against chronic stress in a subject and treating stress sensitive disorders in a subject by antagonizing ghrelin or ghrelin receptor.
1. A method of protecting against stress-sensitive disorders associated with chronic stress in a subject in need thereof, comprising
administering to the subject a therapeutically effective amount of an agent that reduces the level or activity of ghrelin or ghrelin receptor, compared to before the agent is administered,
wherein the agent is a growth hormone secretagogue receptor 1a (GHSr1a) antagonist, a GHSr1a inverse agonist, an enzyme that deacylates ghrelin, or an agent that inhibits the activity of ghrelin O-acyltransferase (GOAT); and
wherein the stress-sensitive disorder is selected from the group consisting of: post-traumatic stress disorder (PTSD), depressive disorder, major depressive disorders, bipolar disorder, acute stress disorder, generalized anxiety disorder, obsessive-compulsive disorder, social anxiety disorders, panic disorders, phobias, and trichotillomania.
2. The method of claim 1 wherein the agent is administered before, during and/or after exposure of the subject to chronic stress.
3. The method of claim 1 wherein the agent is a GHSr1a antagonist or a GHSr1a inverse agonist.
4. The method of claim 1 wherein the agent is an anti-ghrelin vaccine.
5. The method of claim 1 wherein the agent inhibits the activity of GOAT.
6. The method of claim 5 , wherein the agent is an anti-GOAT vaccine.
7. The method of claim 1 , wherein the agent is an enzyme that deacylates ghrelin.
8. The method of claim 1 , wherein the chronic stress is associated with military service or a natural disaster.
9. The method of claim 7 , wherein the enzyme that deacylates ghrelin is an esterase.
10. The method of claim 9 , wherein the esterase is acyl protein thioesterase 1 (APT1).