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Involvement of 5 -HT1D receptors in cortical extracellular 5-HT release in guinea-pigs on exposure to the elevated plus maze

Present address: Institute of Pharmacology and Toxicology, Humboldt-University at Berlin, D-10098 Berlin, Germany

H. Fink

Institute of Pharmacology and Toxicology, Humboldt-University at Berlin, D-10098 Berlin, Germany

M. Skingle

External Scientific Affairs, Glaxo Research and Development Ltd, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK

C.A. Marsden

Department of Physiology and Pharmacology, University of Nottingham Medical School, Queeris Medical Centre, Nottingham NG7 2UH UK

Previous studies have shown that guinea-pigs handled daily from birth exhibit on exposure to the elevated plus maze similar behaviour to rats and increased cortical extracellular 5-HT determined by in vivo microdialysis. The present study investigates the effects of a non-selective 5-HT₁ agonist 5-carboxamidotryptamine (5-CT) and the 5-HT_1D antagonist GR 127935 on behaviour and the release of cortical extracellular 5-HT both in a familiar environment and on exposure to the elevated plus maze. In the familiar environment of the home cage GR 127935 (0.3mg/kg i.p.) had no effect on extracellular 5-HT. The non-selective agonist 5-CT (0.1 mg/kg i.p) produced a prolonged decrease (-25%) in cortical 5-HT release, an effect noT antagonized by GR 127935 (0.3mg/kg). Under aversive conditions, exposure to the elevated plus maze, the release of extracellular 5-HT increased (155% of basal release), an effect abolished by 5-CT. Pre-treatment with the selective 5.HT_1D antagonist GR 127935 antagonized the effect of 5-CT on the aversion-induced increase in extracellular 5-HT on exposure to the elevated plus maze, but did not change the effects of 5-CT on basal 5-HT release. The results suggest that GR 127935 is an effective antagonist at the 5 -HT_1D terminal autoreceptor in vivo under conditions of increased 5- HT function. Furthermore, the results indicate that the 5-HT _1D receptor in the frontal cortex is functionally active under aversive conditions.

Key Words: 5-HT • 5 -HT1D antagonist • GR 127935 • aversion • X-maze • guinea-pig

Journal of Psychopharmacology, Vol. 10, No. 3, 219-224 (1996)
DOI: 10.1177/026988119601000307


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