Acute anxiogenic-like effects of selective serotonin reuptake inhibitors are attenuated by the benzodiazepine diazepam in BALB/c mice

Melissa A Birkett Greene, Nina M. Shinday, Eileen J. Kessler, Jerrold S. Meyer, Sarah Ritchie, James K. Rowlett

Research output: Contribution to journalArticle

31 Scopus citations


Selective serotonin re-uptake inhibitors (SSRIs), which are used commonly to treat anxiety disorders, have characteristic anxiogenic effects following acute administration. Treatment with anxiolytic benzodiazepines (BZs) may reduce these effects, although little is known about potential drug interactions. Our study evaluated acute anxiogenic-like effects of SSRIs, alone and combined with a BZ. Adult male BALB/c mice received fluoxetine (3.0-30.0 mg/kg, i.p.) or citalopram (3.0-30.0 mg/kg, i.p.) alone or in combination with diazepam (0.3-10.0 mg/kg, i.p.), after which they were evaluated with the light/dark and open-field tests for anxiogenesis/anxiolysis. In addition, release of the stress hormone corticosterone was assessed following combined SSRI/BZ administration. In the light/dark and open-field tests, acute SSRIs produced a behavioral profile consistent with anxiogenesis, while diazepam produced an anxiolytic-like profile. Pre-treatment with diazepam (0.3-10 mg/kg) reversed the effects of an anxiogenic-like dose of an SSRI (18 mg/kg fluoxetine, 30 mg/kg citalopram) in both light/dark and open-field tests. Diazepam, fluoxetine or citalopram, and their combination all significantly increased plasma corticosterone levels to the same degree. These findings suggest that a BZ-type drug can attenuate acute anxiogenic-like effects of an SSRI via a mechanism independent of corticosterone regulation.

Original languageEnglish (US)
Pages (from-to)544-551
Number of pages8
JournalPharmacology Biochemistry and Behavior
Issue number4
StatePublished - Jun 2011
Externally publishedYes



  • Anxiety
  • Benzodiazepine
  • Corticosterone
  • Light/dark
  • Mouse
  • Open field
  • SSRI

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology
  • Toxicology
  • Behavioral Neuroscience
  • Biological Psychiatry

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