title: Involvement of vasopressin 3 receptors in chronic psychological stress-induced visceral hyperalgesia in rats.
abstract: Visceral hypersensitivity and stress have been implicated in the pathophysiology of functional gastrointestinal disorders. We used a selective vasopressin 3 (V(3)) receptor antagonist SSR149415 to investigate the involvement of the vasopressin (AVP)/V(3) signaling system in the development of stress-induced visceral hyperalgesia in rats. Rats were exposed to a daily 1-h session of water avoidance stress (WAS) or sham WAS for 10 consecutive days. The visceromotor response to phasic colorectal distension (CRD, 10-60 mmHg) was assessed before and after stress. Animals were treated daily with SSR149415 (0.3, 1, or 3 mg/kg ip 30 min before each WAS or sham WAS session), with a single dose of SSR149415 (1 mg/kg ip), or the selective corticotropin-releasing factor 1 (CRF(1)) antagonist DMP-696 (30 mg/kg po) before CRD at day 11. Effects of a single dose of SSR149415 (10 mg/kg iv) on acute mechanical sensitization during repetitive CRD (12 distensions at 80 mmHg) were also assessed. In vehicle-treated rats, repeated WAS increased the response to CRD, indicating visceral hypersensitivity. Repeated administration of SSR149415 at 1 or 3 mg/kg completely prevented stress-induced visceral hyperalgesia. Similarly, a single dose of DMP-696 or SSR149415 completely blocked hyperalgesic responses during CRD. In contrast, a single dose of SSR149415 did not affect the acute hyperalgesic responses induced by repeated, noxious distension. These data support a major role for V(3) receptors in repeated psychological stress-induced visceral hyperalgesia and suggest that pharmacological manipulation of the AVP/V(3) pathway might represent an attractive alternative to the CRF/CRF(1) pathway for the treatment of chronic stress-related gastrointestinal disorders.
authors.affiliation: University of California Los Angeles Center for Neurobiology of Stress, Departments of Medicine, Physiology, and Psychiatry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90073. sbradesi@ucla.edu
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bradesi
authors.forename: Vicente
authors.initials: V
authors.lastname: Martinez
authors.forename: Lijun
authors.initials: L
authors.lastname: Lao
authors.forename: Håkan
authors.initials: H
authors.lastname: Larsson
authors.forename: Emeran A
authors.initials: EA
authors.lastname: Mayer
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000378:metabolism; D002908:Chronic Disease; D003106:Colon / Q000294:innervation / Q000378:metabolism*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage; D006930:Hyperalgesia / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control / Q000523:psychology; D007211:Indoles / Q000008:administration & dosage; D008297:Male; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D017288:Pain Threshold; D011312:Pressure; D011720:Pyrazoles / Q000008:administration & dosage; D011759:Pyrrolidines / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000378:metabolism*; D013315:Stress, Psychological / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D014227:Triazines / Q000008:administration & dosage; D000099052:CRF Receptor, Type 1
chemical_list: C456029:1-(5-chloro-1-((2,4-dimethoxyphenyl)sulfonyl)-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl)-4-hydroxy-N,N-dimethyl-2-pyrrolidinecarboxamide; D065092:Antidiuretic Hormone Receptor Antagonists; C404928:DMP 696; D005765:Gastrointestinal Agents; D007211:Indoles; D011720:Pyrazoles; D011759:Pyrrolidines; D018019:Receptors, Corticotropin-Releasing Hormone; D017483:Receptors, Vasopressin; D014227:Triazines; D001127:Arginine Vasopressin; D000099052:CRF Receptor, Type 1