The cortical projection of the dorsal raphe nucleus: some electrophysiological and pharmacological properties.

The effect of repetitive stimulation of the dorsal raphe nucleus (DRN) on the firing of spontaneously active neurons of the rostral and posterior cingulate cortex was investigated in untreated and serotonin-depleted rats under chloral hydrate anesthesia. In the untreated animals, the action of microiontophoretically administered serotonin (5-HT) on cell firing was compared with the transsynaptically elicited effects. In the untreated animals, the main transsynaptic effect on neurons of all cell layers of both the rostral and cingulate cortex was an inhibitory one. In the cingulate cortex 50-70% of the neurons were depressed, and in the rostral cortex 30-60% responded with a temporary arrest of their discharge frequency to DRN stimulation. In contrast, only 5-10% of frontal neurons and 0-5% of the cingulate neurons were activated under these conditions. The inhibitory, transsynaptic effect on cingulate and rostral cortical cells was mimicked im most instances by microiontophoretically administered 5-HT. In the cingulate cortex 92% of the neurons and in the rostral cortex 70% of the neurons inhibited by DRN stimulation were depressed by locally administered 5-HT. The majority of the neurons activated by DRN stimulation were also depressed by microiontophoretically applied 5-HT. Furthermore, some 75% of the neurons in the cingulate and some 47% of all neurons tested in the rostral cortex that were not inhibited by DRN stimulation, were also depressed by microiontophoretically applied 5-HT. The peripheral 5-HT antagonists methysergide, cyproheptadine and GP 50 302, administered intraperitoneally, were found to be potent antagonists of transsynaptically elicited inhibitory effects in the cingulate cortex. The depressant action of microiontophoretically administered 5-HT on cingulate cortical neurons was antagonized by all three microiontophoretically administered 5-HT antagonists. In conclusion, the results of the present study are in keeping with recent anatomical observations demonstrating that the entire cortex is densely innervated by 5-HT axons reaching all cell layers. It is shown that these fibers exert an inhibitory influence on the activity of a high percentage of neurons in different layers of the rostral and cingulate cortex.