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

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-HT(1) 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.