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5-HT 1A receptors and changes in extracellular 5-HT in the guinea-pig prefrontal cortex: involvement in aversive behaviour

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

C.A. Marsden

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

H. Fink

Institute of Pharmacology and Toxicology, Humboldt University, 10098 Berlin, Germany

The study demonstrates that guinea-pigs handled daily from birth exhibit similar behaviour to rats on the elevated plus maze. Simultaneously performed intra-cortical microdialysis showed that placing guinea-pigs on the elevated plus maze results in an increase in extracellular 5-HT in the frontal cortex. 8-OH-DPAT (0.3 mg/kg s.c.) reduced significantly the increase in cortical extracellular 5-HT and resulted in an 'anxiolytic' profile of behaviour. Pre-treatment with the 5-HT₁ antagonist methiothepin (10.0 mg/kg) antagonized the behavioural effects and prevented the increase in cortical extracellular 5-HT normally produced by exposure to the elevated plus maze. Methiothepin alone had no effect on behaviour in the elevated plus maze. 5-CT (0.1 mg/kg i.p.) abolished the rise in extracellular 5-HT, but did not produce an 'anxiolytic' profile of behaviour on the elevated plus maze. The results show that an increase in cortical extracellular 5-HT occurs in the saline- treated guinea-pig exposed to aversive conditions. It remains to be determined whether the 'anxiolytic' effect of 8-OH-DPAT in the guinea-pig is causally associated with decreased basal extracellular 5-HT. The results however indicate that there is no simple relationship between inhibition of 5-HT release and behaviour indicative of 'anxiolytic' drug actions.

Key Words: 5-HT • X-maze • 8-OH-DPAT • 5-CT • methiothepin • guinea-pig

Journal of Psychopharmacology, Vol. 7, No. 4, 338-345 (1993)
DOI: 10.1177/026988119300700405


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				A. Rex, H. Fink, M. Skingle, and C.A. Marsden Involvement of 5 -HT1D receptors in cortical extracellular 5-HT release in guinea-pigs on exposure to the elevated plus maze J Psychopharmacol, January 1, 1996; 10(3): 219 - 224. [Abstract] [PDF]