SSR149415, a non-peptide vasopressin V1b receptor antagonist, has long-lasting antidepressant effects in the olfactory bulbectomy-induced hyperactivity depression model

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

Research output: Contribution to journalArticleAcademicpeer-review

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 1(b) (V-1b) receptor and the development of depression has been suggested; therefore, a vasopressin V-1b 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 V-1b receptor antagonist may have long-lasting antidepressant activity.

Original languageEnglish
Pages (from-to)101-106
Number of pages6
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume379
Issue number1
DOIs
Publication statusPublished - 1 Jan 2009
Externally publishedYes

Keywords

  • Depression
  • Olfactory bulbectomy
  • Rat
  • SSR149415
  • V1b receptor
  • Vasopressin
  • nelivaptan
  • imipramine
  • vasopressin receptor antagonist
  • vasopressin V1b receptor
  • acute drug administration
  • adrenal gland
  • animal experiment
  • animal model
  • article
  • chronic drug administration
  • controlled study
  • depression
  • hyperactivity
  • male
  • nonhuman
  • olfactory bulbectomy
  • open field behavior
  • rat
  • treatment response

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