Elsevier

Neuropharmacology

Volume 36, Issues 4–5, April–May 1997, Pages 577-588
Neuropharmacology

In Vivo Electrophysiological Characterization of 5-HT Receptors in the Guinea Pig Head of Caudate Nucleus and Orbitofrontal Cortex

https://doi.org/10.1016/S0028-3908(97)00035-XGet rights and content

Abstract

The aim of the present study was to characterize in vivo the 5-HT receptor 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 preferential 5-HT2C receptor agonist mCPP, suppressed the quisqualate (QUIS)-induced activation of neurons in both structures. The inhibitory effect of DOI and mCPP was not prevented by acute intravenous administration of the 5-HT12 receptor antagonist metergoline (2 mg/kg) and the 5-HT2A/2C receptor antagonist ritanserin (2 mg/kg) in the two regions nor by the selective 5-HT2A receptor antagonist MDL100907 (1 mg/kg) in the head of caudate nucleus. However, the inhibitory effect of DOI, but not that of mCPP, was antagonized by a 4-day treatment with metergoline and ritanserin (2 mg/kg/day; using minipumps implanted subcutaneously) in head of caudate nucleus, but not in orbitofrontal cortex. Microiontophoretic ejection of the 5-HT1A/7 receptor agonist 8-OH-DPAT and of the 5-HT1A receptor antagonist WAY100635 both suppressed the spontaneous and QUIS-activated firing activity of orbitofrontal cortex neurons. At currents which did not affect the basal discharge activity of the neuron recorded, microiontophoretic application of WAY100635 and BMY7378 failed to prevent the inhibitory effect of 8-OH-DPAT. The inhibitory effect of gepirone, which is a 5-HT1A receptor agonist but devoid of affinity for 5-HT7 receptors, was also not antagonized by WAY100635. Altogether, these results suggest the presence of atypical 5-HT1A receptors in the orbitofrontal cortex. The present results also indicate that the suppressant effect of DOI may be mediated by 5-HT2A receptors in head of caudate nucleus and atypical 5-HT2 receptors in orbitofrontal cortex. © 1997 Elsevier Science Ltd.

Section snippets

Treatments

Male guinea pigs (250–300 g) were anesthetized with halothane and implanted with an osmotic minipump subcutaneously (Alza, Palo Alto, CA, U.S.A.) that delivered the 5-HT2 receptor antagonists metergoline or ritanserin (2 mg/kg/day) or 0.9% NaCl in the controls.

Single unit recording and microiontophoresis

Guinea pigs were anesthetized with chloral hydrate (200 mg/kg, i.p. followed by subsequent 50 mg/kg doses approximately every 30 min to achieve complete anesthesia) and placed in a stereotaxic frame. Body temperature was maintained at

RESULTS

Most caudate neurons were either quiescent or fired at extremely slow rate and were, therefore, activated by microiontophoretic application of QUIS. Since the average basal firing rate of spontaneously active caudate cells has been estimated at 4–6 spikes/sec (El Mansari et al., 1994), the ejection current of QUIS was set to activate quiescent cells to about this rate generally with currents of 80–100 nA. The average basal firing rate of spontaneously active orbitofrontal neurons was estimated

DISCUSSION

The present study was aimed at characterizing the 5-HT receptor subtypes mediating the effect of microiontophoretic ejection of 5-HT in the guinea pig head of caudate nucleus and orbitofrontal cortex. The inhibitory effect of 5-HT and of the 5-HT2 receptor agonists DOI and mCPP was not antagonized by acute intravenous administration of the 5-HT2 receptor antagonists metergoline and ritanserin, in the head of caudate nucleus. However, after a 4 day treatment with metergoline and ritanserin, the

Acknowledgements

This study was supported by the Medical Research Council of Canada grant MA-11014 and a Scientist awarded to P.B. and the Fonds de la Recherche en Santé du Québec (FRSQ). M.E. was in receipt of postdoctoral fellowship from the FRSQ.

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