IN-VIVO ELECTROPHYSIOLOGICAL CHARACTERIZATION OF 5-HT RECEPTORS IN THE GUINEA-PIG HEAD OF CAUDATE-NUCLEUS AND ORBITOFRONTAL CORTEX

The aim of the present study was to characterize in vivo the 5-HT rece ptor subtypes which mediate the effect of microiontophoretic applied 5 -HT in the guinea pig head of caudate nucleus and orbitofrontal cortex . 5-HT and the preferential 5-HT2A receptor agonist DOI and the prefer ential 5-HT2C receptor agonist mCPP, suppressed the quisqualate (QUIS) -induced activation of neurons in both structures. The inhibitory effe ct of DOI and mCPP was not prevented by acute intravenous administrati on of the 5-HT1/2 receptor antagonist metergoline (2 mg/kg) and the 5- HT2A/2C receptor antagonist ritanserin (2 mg/kg) in the two regions no r by the selective 5-HT2A receptor antagonist MDL100907 (1 mg/kg) in t he head of caudate nucleus. However, the inhibitory effect of DOI, but not that of mCPP, was antagonized by a 4-day treatment with metergoli ne and ritanserin (2 mg/kg/day; using minipumps implanted subcutaneous ly) in head of caudate nucleus, but not in orbitofrontal cortex. Micro iontophoretic ejection of the 5-HT1A/7 receptor agonist 8-OH-DPAT and of the 5-HT1A receptor antagonist WAY100635 both suppressed the sponta neous and QUIS-activated firing activity of orbitofrontal cortex neuro ns. At currents which did not affect the basal discharge activity of t he neuron recorded, microiontophoretic application of WAY100635 and BM Y7378 failed to prevent the inhibitory effect of 8-OH-DPAT. The inhibi tory effect of gepirone, which is a 5-HT1A receptor agonist but devoid of affinity for 5-HT7 receptors, was also not antagonized by WAY10063 5. Altogether, these results suggest the presence of atypical 5-HT1A r eceptors in the orbitofrontal cortex. The present results also indicat e that the suppressant effect of DOI may be mediated by 5-HT2A recepto rs in head of caudate nucleus and atypical 5-HT2 receptors in orbitofr ontal cortex. (C) 1997 Elsevier Science Ltd.