Abstract
Diazepam (5 mg/kg) increased the number of shocks accepted by rats on two successive trials in the punished drinking test. Thus, the phenomenon of “one trial tolerance” to the anxiolytic effects of benzodiazepines in the elevated plus-maze does not generalise to this other animal test of anxiety. FG 7142 (20 mg/kg) and prior exposure to the odour of a cat had significant anxiogenic effects on two successive trials in the plus-maze. Thus the phenomenon of “one trial tolerance” does not generalise to these anxiogenic effects in the plus-maze. Furthermore, chlordiazepoxide retained its ability to counteract the anxiogenic effects in the plus-maze of prior exposure to cat odour, over successive trials. On the basis of these and previous experiments it is suggested that the state of anxiety generated on trial 2 in the plus-maze is close to a phobic state, against which benzodiazepines are relatively ineffective. Chlordiazepoxide (5 and 10 mg/kg) was also ineffective against the behavioural responses of rats during exposure to cat odour, another possible animal test of phobia. This contrasted with its efficacy against the anxiogenic effects of cat odour that subsequently generalised to and could be detected in the plus-maze.
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References
Blanchard DC, Hori K, Rodgers RJ, Hendrie CA, Blanchard RJ (1989) Attenuation of defensive threat and attack in wild rats (Rattus rattus) by benzodiazepines. Psychopharmacology 97:392–401
Blanchard RJ, Blanchard DC, Weiss SM, Meyer S (1990) The effects of ethanol and diazepam on reactions to predatory odours. Pharmacol Biochem Behav 35:775–780
File SE (1990a) One-trial tolerance to the anxiolytic effects of chlordiazepoxide in the plus-maze. Psychopharmacology 100:281–282
File SE (1990b) The history of benzodiazepine dependence: a review of animal studies. Neurosci Biobehav Rev 14:135–146
File SE, Mabbutt PS, Hitchcott PK (1990) Characterisation of the phenomenon of “one-trial tolerance” to the anxiolytic effect of chlordiazepoxide in the elevated plus-maze. Psychopharmacology 102:98–101
File SE, Andrews N, Wu PY, Zharkovsky A, Zangrossi H (1992) Modification of chlordiazepoxide's behavioural and neurochemical effects by handling and plus-maze experience. Eur J Pharmacol (in press)
Lister RG (1987) The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology 92:180–185
Lister RG (1991) Ethologically based animal models of anxiety disorders. In: File SE (ed) Psychopharmacology of anxiolytics and antidepressants. Pergamon Press, New York, pp 155–185
Howard JL, Pollard GT (1991) Effects of drugs on punished behaviour: pre-clinical test for anxiolytics. In: File SE (ed) Psychopharmacology of anxiolytics and antidepressants. Pergamon Press, New York, pp 131–153
Marks IM (1987) Fears, phobias and rituals. Oxford University Press, New York
Mineka S (1985) Animal models of anxiety-based disorders. In: Tuma AH, Maser JD (eds) Anxiety and anxiety disorders. Erlbaum, Hillsdale, pp 199–244
Rodgers RJ, Lee C, Shepherd JK (1992) Effects of diazepam on behavioural and antinociceptive responses to the elevated plusmaze in male mice depend upon treatment regimen and prior maze experience. Psychopharmacology 106:102–110
Pellow S, File SE (1986) Anxiolytic and anxiogenic drug effects in exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacol Biochem Behav 24:525–529
Zangrossi H, File SE (1992) Behavioral consequences in animal tests of anxiety and exploration of exposure to cat odor. Brain Res Bull (in press)
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File, S.E., Zangrossi, H. “One-trial tolerance” to the anxiolytic actions of benzodiazepines in the elevated plus-maze, or the development of a phobic state?. Psychopharmacology 110, 240–244 (1993). https://doi.org/10.1007/BF02246980
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DOI: https://doi.org/10.1007/BF02246980