SSR149415, a non-peptide vasopressin V1b receptor antagonist, has long-lasting antidepressant effects in the olfactory bulbectomy-induced hyperactivity depression model |
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Authors: | M E Breuer M M van Gaalen W Wernet S E F Claessens R S Oosting B Behl S M Korte H Schoemaker G Gross B Olivier L Groenink |
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Institution: | (1) Department of Psychopharmacology, Utrecht University, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands;(2) Department of Pharmacology and Anatomy, Section Behavioral Genomics, Rudolf Magnus Institute of Neuroscience, Utrecht, The Netherlands;(3) Neuroscience Research, GPRD, Abbott, Ludwigshafen, Germany;(4) Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA |
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Abstract: | Olfactory bulbectomy (OBX) in rats causes several behavioral and neurochemical CNS changes, reminiscent of symptoms of human
depression. Such depression-like behavior after OBX can be reversed with antidepressants. Recently, a connection between the
vasopressin 1b (V1b) receptor and the development of depression has been suggested; therefore, a vasopressin V1b receptor antagonist (SSR149415) was investigated in the OBX model. Male rats received olfactory bulbectomy or sham surgery.
After recovery, animals received 14 consecutive daily doses of SSR149415 (10 or 30 mg/kg), imipramine (20 mg/kg), or vehicle
(5% hydroxy-propyl methylcellulose). Animals were tested in an open field after acute treatment, on days 7 and 14 of treatment
and 1 week after cessation of treatment. Similar to imipramine, repeated, but not acute, administration of SSR149415 completely
reversed OBX-induced hyperactivity, leaving activity in shams unaffected. This reversal of OBX-induced hyperactivity in the
SSR149415 treated rats was still present 7 days after cessation of treatment. Although the behavioral effects of treatment
with SSR149415 were specific for the OBX animals, adrenal gland weights were reduced in both sham and OBX animals treated
with 30 mg/kg SSR149415. Chronic but not acute administration of SSR149415 normalizes OBX-induced hyperactivity up to 1 week
after cessation of treatment, suggesting that a V1b receptor antagonist may have long-lasting antidepressant activity. |
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Keywords: | Olfactory bulbectomy V1b receptor Depression Vasopressin SSR149415 Rat |
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