Recent observations made in our laboratory have shown that metergoline is a selective 5-hydroxytryptamine (5-HT) antagonist in the cerebral cortex. Fluoxetine is a reportedly selective 5-HT neuronal uptake blocker. In the present investigation these drugs have been used to examine the existence of a putative 5-HT input to the cerebral cortex. In rats anaesthetized with a mixture of methoxyflurane, nitrous oxide, and oxygen, stimulation of the median raphé nucleus or of the ipsilateral cortical surface and iontophoretically applied 5-HT decreased the firing of the deep cerebral cortical neurones. Metergoline antagonized the 5-HT-induced depression and reduced the duration of inhibition produced by raphé nucleus stimulation. These results suggest that the cerebral cortical neurones are inhibited by an ascending 5-HT-containing pathway.
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