Serotonergic innervation of the locus coeruleus from the dorsal raphe and its action on responses to noxious stimuli.

The connexions between the dorsal raphe nucleus and the nucleus locus coeruleus were studied in urethane anaesthetized rats. 1. Cells in the locus coeruleus gave an excitatory response to a noxious stimulus, e.g. leg pinch. 2. This excitatory response was blocked by either a parenteral or an ionophoretic injection of morphine and recovered after an injection of naloxone. 3. Electrical stimulation in the region of the dorsal raphe blocked excitatory locus coeruleus responses to noxious stimuli. 4. While naloxone did not antagonize the effects of the dorsal raphe stimulation towards locus coeruleus activity, these effects were absent in rats pretreated with a serotonin synthesis inhibitor, PCPA or with 5,7-DHT which destroys serotonin-containing terminals, and were reduced by the serotonin antagonist methysergide. 5. A serotonin-containing inhibitory pathway between the dorsal raphe and the locus coeruleus is proposed to account for these results.