Skip to main content
SpringerLink
Log in

Validation of a modified mirrored chamber sensitive to anxiolytics and anxiogenics in mice

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Anxiety is a common disorder in humans that exists in many forms, and animal models of human anxiety are typically employed for the discovery of anxiolytic drugs with human therapeutic potential.

Objectives

Ideally, animal models of anxiety are validated for the detection of both anxiogenic and anxiolytic effects, but most animal models can effectively only measure anxiolytic-like effects. As control animals typically spend small amounts of time in the aversive portion of an apparatus, decreases in time spent in this portion are difficult to detect.

Methods

We have modified an existing test of murine anxiety, the mirrored chamber, and have validated this test using several anxiolytic and anxiogenic drugs. In addition, nine mouse strains were compared on the elevated plus maze and modified mirrored chamber.

Results

Increasing doses of ethanol, diazepam, and pentobarbital produced an anxiolytic-like profile while pentylenetetrazol (PTZ), d-amphetamine, and methyl-6, 7-dimethoxyl-4-ethyl-beta-carboline-3-carboxylate (DMCM) appeared anxiogenic. This modified test also dissociated drug effects on anxiety from those on activity for d-amphetamine and diazepam. The inbred mouse strains tested produced a similar range of scores for time spent on the open arms of the elevated plus maze and voluntary reentry time in the mirrored chamber, with an overall genetic correlation of 0.68.

Conclusions

Since control animals reliably reentered the more aversive portion of the apparatus for 25% of the total time available, the modified mirrored chamber may be able to detect anxiogenic states produced by various stressors and drug withdrawal. Further, the strain differences detected suggest that the modified mirrored chamber will be a valuable tool in the discovery of the genetic bases of anxiety states and disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.

Similar content being viewed by others

References

  • Belzung C, Griebel G (2001) Measuring normal and pathological anxiety-like behaviour in mice: a review. Behav Brain Res 125:141–149

    CAS  PubMed  Google Scholar 

  • Boehm SL II, Reed CL, McKinnon CS, Phillips TJ (2002) Shared genes influence sensitivity to the effects of ethanol on locomotor and anxiety-like behaviors, and the stress axis. Psychopharmacology 161:54–63

    Article  CAS  PubMed  Google Scholar 

  • Bowers BJ, Elliott KJ, Wehner JM (2001) Differential sensitivity to the anxiolytic effects of ethanol and flunitrazepam in PKCγ null mutant mice. Pharmacol Biochem Behav 69:99–110

    Article  CAS  PubMed  Google Scholar 

  • Clement Y, Calatayud F, Belzung C (2002) Genetic basis of anxiety-like behaviour: a critical review. Brain Res Bull 57:57–71

    Article  PubMed  Google Scholar 

  • Cole BJ, Hillmann M, Seidelmann D, Klewer M, Jones GH (1995) Effects of benzodiazepine receptor partial inverse agonists in the elevated plus maze test of anxiety in the rat. Psychopharmacology 121:118–126

    CAS  PubMed  Google Scholar 

  • Crabbe JC, Kosobud A, Young ER (1983) Genetic selection for ethanol withdrawal severity: differences in replicate mouse lines. Life Sci 33:955–962

    Article  CAS  PubMed  Google Scholar 

  • Crawley J, Goodwin FK (1980) Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines. Pharmacol Biochem Behav 13:167–170

    CAS  Google Scholar 

  • Davis WM, Babbini M, Pong SF, King WT, White CL (1974) Motility of mice after amphetamine: effects of strain, aggregation and illumination. Pharmacol Biochem Behav 2:803–809

    Article  CAS  PubMed  Google Scholar 

  • Dawson GR, Crawford SP, Collinson N, Iversen SD, Trickleback MD (1995) Evidence that the anxiolytic-like effects of chlordiazepoxide on the elevated plus maze are confounded by increases in locomotor activity. Psychopharmacology 118:316–323

    Google Scholar 

  • Freeman MP, Freeman SA, McElroy SL (2002) The comorbidity of bipolar and anxiety disorders: prevalence, psychobiology, and treatment issues. J Affect Disord 68:1–23

    Article  PubMed  Google Scholar 

  • Gallup GG Jr (1968) Mirror-image stimulation. Psychol Bull 70:782–783

    PubMed  Google Scholar 

  • Geller I, Seifter J (1960) The effects of meprobamate, barbiturates, d-amphetamine, and promazine on experimentally induced conflict in the rat. Psychopharmacologia 1:482–492

    CAS  Google Scholar 

  • Gillespie NA, Zhu G, Heath AC, Hickie IB, Martin NG (2000) The genetic aetiology of somatic distress. Psychol Med 30:1051–1061

    Article  CAS  PubMed  Google Scholar 

  • Hascoët M, Bourin M (1998) A new approach to the light/dark test procedure in mice. Pharmacol Biochem Behav 60:645–653

    Article  PubMed  Google Scholar 

  • Houri D (1986) Effects of central acting drugs on the mirror staircase test. Nippon Yakurigaku Zasshi 87:135–142

    CAS  PubMed  Google Scholar 

  • Jung ME, Wallis CJ, Gatch MB, Lal H (2000) Abecarnil and alprazolam reverse anxiety-like behaviors induced by ethanol withdrawal. Alcohol 21:161–168

    Article  CAS  PubMed  Google Scholar 

  • Lin HQ, Burden PM, Christie MJ, Johnston AR (1999) The anxiogenic-like and anxiolytic-like effects of MDMA on mice in the elevated plus-maze: a comparison with amphetamine. Pharmacol Biochem Behav 62:403–408

    CAS  PubMed  Google Scholar 

  • Lister RG (1987) The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology 92:180–185

    CAS  PubMed  Google Scholar 

  • Pahkla R, Kask A, Rago L (2000) Differential effects of beta-carbolines and antidepressants on rat exploratory activity in the elevated zero-maze. Pharmacol Biochem Behav 65:737–742

    Article  CAS  PubMed  Google Scholar 

  • Pellow S, Chopin P, File SE, Briley M (1985) Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Meth 14:149–167

    CAS  PubMed  Google Scholar 

  • Quartermain D, Stone EA, Charbonneau G (1996) Acute stress disrupts risk assessment behavior in mice. Physiol Behav 59:937–940

    Article  CAS  PubMed  Google Scholar 

  • Reddy DS, Kulkarni SK (1997) Differential anxiolytic effects of neurosteroids in the mirrored chamber behavior test in mice. Brain Res 752:61–71

    Article  CAS  PubMed  Google Scholar 

  • Rigon AR, Takahashi RN (1996) Stimulant activities of dimethocaine in mice: reinforcing and anxiogenic effects. Psychopharmacology 127:323–327

    Article  CAS  PubMed  Google Scholar 

  • Rodgers RJ, Cole JC, Aboualfa K, Stephenson LH (1995) Ethopharmacological analysis of the effects of putative 'anxiogenic' agents in the mouse elevated plus-maze. Pharmacol Biochem Behav 52:805–813

    CAS  PubMed  Google Scholar 

  • Seale TW, Niekrasz I, Garrett KM (1996) Anxiolysis by ethanol, diazepam and buspirone in a novel murine behavioral assay. Neuroreport 7:1803–1808

    CAS  PubMed  Google Scholar 

  • Sokal RR, Rohlf FJ (1981) Biometry, 2nd edn. W.H. Freeman, New York

  • Toubas PL, Abla KA, Cao W, Logan LG, Seale TW (1990) Latency to enter a mirrored chamber: a novel behavioral assay for anxiolytic agents. Pharmacol Biochem Behav 35:121–126

    Article  CAS  PubMed  Google Scholar 

  • Trullas R, Skolnick P (1993) Differences in fear motivated behaviors among inbred mouse strains. Psychopharmacology 111:323–331

    CAS  PubMed  Google Scholar 

  • Turri MG, Datta SR, DeFries J, Henderson ND, Flint J (2001) QTL analysis identifies multiple behavioral dimensions in ethological tests of anxiety in laboratory mice. Curr Biol 11:725–734

    Article  CAS  PubMed  Google Scholar 

  • Van Gaalen MM, Steckler T (2000) Behavioural analysis of four mouse strains in an anxiety test battery. Behav Brain Res 115:95–106

    PubMed  Google Scholar 

  • Vogel JR, Beer B, Clody DE (1971) A simple and reliable procedure for testing anti-anxiety agents. Psychopharmacology 21:1–7

    Google Scholar 

  • Voikar V, Koks S, Vasar E, Rauvala H (2001) Strain and gender differences in the behavior of mouse lines commonly used in transgenic studies. Physiol Behav 72:271–281

    CAS  PubMed  Google Scholar 

  • Weiss SM, Wadsworth G, Fletcher A, Dourish CT (1998) Utility of ethological analysis to overcome locomotor confounds in elevated maze models of anxiety. Neurosci Biobehav Rev 23:265–271

    Article  CAS  PubMed  Google Scholar 

  • Wilson J, Watson WP, Little HJ (1998) CCK(B) antagonists protect against anxiety-related behaviour produced by ethanol withdrawal, measured using the elevated plus maze. Psychopharmacology 137:120–131

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge Dr. Tamara J. Phillips, Dr. Pamela Metten, and Nathan Rustay for comments on experiments, and Chia-Hua Yu and Alisha Ketner for technical assistance. This research was supported by two VA Merit Review grants, NIAAA grants T32AA07468 and P50AA10760, and NIDA grant DA05288.

Author information

Authors and Affiliations

  1. Department of Behavioral Neuroscience, Portland Alcohol Research Center, Oregon Health & Science University, VAMC Research (R&D 12), Department of Veterans Affairs Medical Center, 3710 SW US Veterans Hospital Road, Portland, OR 97239, USA

    Christopher L. Kliethermes, Deborah A. Finn & John C. Crabbe

Authors
  1. Christopher L. Kliethermes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Deborah A. Finn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John C. Crabbe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christopher L. Kliethermes.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kliethermes, C.L., Finn, D.A. & Crabbe, J.C. Validation of a modified mirrored chamber sensitive to anxiolytics and anxiogenics in mice. Psychopharmacology 169, 190–197 (2003). https://doi.org/10.1007/s00213-003-1493-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-003-1493-z

Keywords

Search

Navigation