title: Antidepressant-like effects of the vasopressin V1b receptor antagonist SSR149415 in the Flinders Sensitive Line rat.
abstract: There is an increased interest in the potential of vasopressin receptor antagonists as antidepressants because of the involvement of vasopressin in stress-related behavioral changes. The present study sought to provide confirmatory evidence for the antidepressant-like effects of the selective vasopressin V1b receptor antagonist SSR149415, which had been previously demonstrated in a variety of animal models. The Flinders Sensitive Line (FSL) rat, a selectively bred animal model of depression, was chronically treated for 14 days with SSR149415 (1, 10, and 30 mg/kg), vehicle, or desipramine (5 mg/kg) as a positive control. Approximately 22-24 h after the last treatment, the rats were exposed to a single 5-min session in a cylinder containing 25 degrees C water and immobility was recorded. A control group of Flinders Resistant Line (FRL) rats was included as a reference group as well as one treated with 10 mg/kg SSR149415. Vehicle-treated FSL rats exhibited much more immobility than the FRL rats, and desipramine-treated FSL rats had much lower scores, as expected. Treatment with SSR149415 reduced immobility in the FSL rats at all doses, but only the higher doses reduced it such that they were no longer different from the FRL rats. In contrast, SSR149415 did not alter the lower immobility of the FRL rats. The social interaction test of anxiety was also examined in the FSL rats, at 20-22 h after the last of the 14 injections. Results showed that the 10 and 30 mg/kg doses of SSR149415 increased the time spent in social interaction in the FSL rats, suggesting anxiolytic effects. These findings confirm the antidepressant-like potential of SSR149415 and suggest that it may also have anxiolytic effects. It is likely that the strategy of testing selective vasopressin V1b receptor antagonists will be fruitful.
authors.affiliation: Department of Psychiatry and Bowles Center for Alcohol Studies, CB 7178, 429 Taylor Bldg., University of North Carolina, Chapel Hill, NC 27599-7178, USA. dhover@med.unc.edu
authors.forename: David H
authors.initials: DH
authors.lastname: Overstreet
authors.forename: Guy
authors.initials: G
authors.lastname: Griebel
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017483:Receptors, Vasopressin / Q000819:agonists*; D013550:Swimming
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; D000928:Antidepressive Agents; D007211:Indoles; D011759:Pyrrolidines; D017483:Receptors, Vasopressin