title: Prototypical anxiolytics do not reduce anxiety-like behavior in the open field in C57BL/6J mice.
abstract: Understanding and effectively treating anxiety disorders are a challenge for both scientists and clinicians. Despite a variety of available therapies, the efficacy of current treatments is still not optimal and adverse side effects can result in non-compliance. Animal models have been useful for studying the underlying biology of anxiety and assessing the anxiolytic properties of potential therapeutics. The open field (OF) is a commonly used assay of anxiety-like behavior. The OF was developed and validated in rats and then transferred to use in the mouse with only limited validation. The present study tests the efficacy of prototypical benzodiazepine anxiolytics, chlordiazepoxide (CDP) and diazepam (DZ), for increasing center time in the OF in C57BL/6J (B6) mice. Multiple doses of CDP and DZ did not change time spent in the center of the OF. Increasing illumination in the OF did not alter these results. The non-benzodiazepine anxiolytic, buspirone (BUSP) also failed to increase center time in the OF while the anxiogenic meta-chlorophenylpiperazine (mCPP) increased center time. Additional inbred mouse strains, BALB/cJ (BALB) and DBA/2J (D2) did not show any change in center time in response to CDP. Moreover, evaluation of CDP in B6 mice in the elevated plus maze (EPM), elevated zero maze (EZM) and light dark assay (LD) did not reveal changes in anxiety-like behavior while stress-induced hyperthermia (SIH) was decreased by DZ. Pharmacokinetic (PK) studies suggest that adequate CDP is present to induce anxiolysis. We conclude that the measure of center time in the OF does not show predictive validity for anxiolysis in these inbred mouse strains.
authors: Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, United States.
authors: Trey
authors: T
authors: Thompson
authors: The Genomics Institute of the Novartis Research Foundation, San Diego, CA, United States.
authors: Laura
authors: L
authors: Grabowski-Boase
authors: Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, United States; Department of Psychiatry, School of Medicine, University of North Carolina, Chapel Hill, NC, United States. Electronic address: lisat@med.unc.edu.
authors: Lisa M
authors: LM
authors: Tarantino
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology
chemical_list: D014151:Anti-Anxiety Agents; D010879:Piperazines; C015068:1-(3-chlorophenyl)piperazine
keywords: Anxiety; Benzodiazepine; C57BL/6J; Mice; Open field