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Effect of diazepam on cortical 5-HT release and behaviour in the guinea-pig on exposure to the elevated plus maze

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Abstract

Previous studies have used the elevated plus maze to test for “anxiolytic” drugs in rats. The present study demonstrates that guinea-pigs handled daily from birth exhibit similar behaviour to rats on the plus maze. Pretreatment with diazepam (1.0 mg/kg) significantly increased the time the animals spent in the open arms and amount of entries into the open arms. Using intra-cortical microdialysis on exposure of the guinea-pig to the elevated plus maze resulted in increased extracellular 5-HT in the frontal cortex. Diazepam reduced, but not significantly, the increase in extracellular 5-HT and produced an “anxiolytic” profile of behaviour. Pretreatment with the benzodiazepine antagonist flumazenil (10.0 mg/kg) fully antagonised the behavioural effects of diazepam. Flumazenil also reduced the effect of diazepam on the increase in extracellular 5-HT observed on exposure of the guinea-pig to the elevated plus maze. Flumazenil alone decreased basal extracellular cortical 5-HT but had no effect on behaviour in the elevated plus maze. The results show that an increase in extracellular 5-HT occurs in the guinea-pig exposed to aversive conditions. While it remains to be determined whether the “anxiolytic” effects of diazepam in the guinea-pig are causally associated with decreased extracellular 5-HT, it is of interest that the selective benzodiazepine antagonist also prevented the increase in basal extracellular 5-HT produced by the exposure to the elevated plus maze but had no effect on behaviour. Results indicate that there is no simple relationship between inhibition of 5-HT release and the “anxiolytic” action of benzodiazepines.

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Author notes

  1. H. Fink

    Present address: Institute of Pharmacology and Toxicology, Humboldt University, P.O. Box 140, 0-1040, Berlin, Federal Republic of Germany

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  1. Department of Physiology and Pharmacology, University of Nottingham Medical School, Queen's Medical Centre, NG7 2UH, Nottingham, UK

    A. Rex, C. A. Marsden & H. Fink

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Rex, A., Marsden, C.A. & Fink, H. Effect of diazepam on cortical 5-HT release and behaviour in the guinea-pig on exposure to the elevated plus maze. Psychopharmacology 110, 490–496 (1993). https://doi.org/10.1007/BF02244657

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  • DOI: https://doi.org/10.1007/BF02244657

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