Advertisement

Psychopharmacology

, Volume 92, Issue 2, pp 180–185 | Cite as

The use of a plus-maze to measure anxiety in the mouse

  • Richard G. Lister
Original Investigations

Abstract

To investigate whether an elevated plus-maze consisting of two open and two closed arms could be used as a model of anxiety in the mouse, NIH Swiss mice were tested in the apparatus immediately after a holeboard test. Factor analysis of data from undrugged animals tested in the holeboard and plus-maze yielded three orthogonal factors interpreted as assessing anxiety, directed exploration and locomotion. Anxiolytic drugs (chlordiazepoxide, sodium pentobarbital and ethanol) increased the proportion of time spent on the open arms, and anxiogenic drugs (FG 7142, caffeine and picrotoxin) reduced this measure. Amphetamine and imipramine failed to alter the indices of anxiety. The anxiolytic effect of chlordiazepoxide was reduced in mice that had previously experienced the plus-maze in an undrugged state. Testing animals in the holeboard immediately before the plus-maze test significantly elevated both the percentage of time spent on the open arms and the total number of arm entries, but did not affect the behavioral response to chlordiazepoxide. The plus-maze appears to be a useful test with which to investigate both anxiolytic and anxiogenic agents.

Key words

Anxiety Plus-maze Mouse Benzodiazepine receptor Stimulants Exploration 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ahtee L, Shillito E (1970) The effect of benzodiazepines and atropine on exploratory behaviour and motor activity of mice. Br J Pharmacol 40:361–371Google Scholar
  2. Briley M, Chopin P, Veigner M (1986) The “plus-maze test of anxiety”: validation in different rat strains and effect of a wide variety of antidepressants. Br J Pharmacol 87:217PGoogle Scholar
  3. Charney DS, Galloway MP, Heninger GR (1984) The effects of caffeine on plasma MHPG, subjective anxiety, autonomic symptoms and blood pressure in healthy humans. Life Sci 35:135–144Google Scholar
  4. Crabbe JC (1983) Sensitivity to ethanol in inbred mice: Genotypic correlations among several behavioral responses. Behav Neurosci 97:280–289Google Scholar
  5. Crawley JN, Davis LG (1982) Baseline exploratory activity predicts anxiolytic response to diazepam in five mouse strains. Brain Res Bull 8:609–612Google Scholar
  6. Dorow R, Horowski R, Paschelke G, Amin M, Braestrup C (1983) Severe anxiety induced by FG 7142, a β-carboline ligand for benzodiazepine receptors. Lancet II:98–99Google Scholar
  7. File SE (1983) Variability in behavioural responses to benzodiazepines in the rat. Pharmacol Biochem Behav 18:303–306Google Scholar
  8. File SE, Hyde JRG (1979) A test of anxiety that distinguishes between the actions of benzodiazepines and those of other minor tranquilisers and of stimulants. Pharmacol Biochem Behav 11:65–69Google Scholar
  9. File SE, Lister RG (1984) Do the reductions in social interaction produced by picrotoxin and pentylenetetrazole indicate anxiogenic actions? Neuropharmacology 23:793–796Google Scholar
  10. File SE, Wardill AG (1975) Validity of head-dipping as a measure of exploration in a modified hole-board. Psychopharmacology 44:53–59Google Scholar
  11. Handley SL, Mithani S (1984) Effects of alpha-adrenoceptor agonists and antagonists in a maze-exploration model of ‘fear’-motivated behaviour. Naunyn-Schmiedeberg's Arch Pharmacol 327:1–5Google Scholar
  12. Montgomery KC (1958) The relation between fear induced by novel stimulation and exploratory behaviour. J Comp Physiol Psychol 48:254–260Google Scholar
  13. Nolan NA, Parkes MW (1973) The effects of benzodiazepines on the behaviour of mice in a hole-board. Psychopharmacology 29:277–288Google Scholar
  14. Pellow S, File SE (1984) Multiple sites of action for anxiogenic drugs: behavioural, electrophysiological and biochemical correlations. Psychopharmacology 83:304–315Google Scholar
  15. 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 Methods 14:149–167Google Scholar
  16. Pohorecky LA (1981) The interaction between alcohol and stress: a review. Neurosci Biobehav Rev 5:209–229Google Scholar
  17. Prado de Carvalho L, Venault P, Rossier J, Chapouthier G (1983) Anxiogenic properties of convulsive agents. Soc Neurosci Abstr 9:128Google Scholar
  18. Robbins T, Iversen SD (1973) A dissociation of the effects of d-amphetamine on locomotor activity and exploration in rats. Psychopharmacology 28:155–164Google Scholar
  19. Sternbach LH (1979) The benzodiazepine story. J Med Chem 22:1–7Google Scholar
  20. Uhde TW, Boulenger JP, Jimerson DC, Post RM (1984) Caffeine: relationship to human anxiety, plasma MHPG and cortisol. Psychopharmacol Bull 20:426–430Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • Richard G. Lister
    • 1
  1. 1.Laboratory of Clinical StudiesNIAAABethesdaUSA

Personalised recommendations