Do serotonin-containing dorsal raphe neurons possess autoreceptors?

The potential role of autoreceptors in regulating the activity of serotonin-containing dorsal raphe (RD) neurons was examined by recording the activity of these neurons under a variety of conditions both in vivo and in vitro in the mouse. RD neurons recorded in vivo displayed the characteristic slow, rhythmic discharge pattern previously described for rat and cat RD cells. The activity of these neurons was suppressed in a dose-dependent manner by tryptophan, LSD and chlorimipramine administered intravenously. The inhibitory effect of tryptophan and chlorimipramine was abolished by pretreatment with p-chlorophenylalanine, while that of LSD was not. There were no significant changes in the spontaneous discharge rate of raphe neurons over time when recorded in vitro, even though tissue serotonin and its metabolite, 5-hydroxyindoleacetic acid, decreased dramatically. Prior depletion of brain serotonin by p-chlorophenylalanine administration resulted in no significant change in RD neuron activity recorded in vitro. Elevation of brain serotonin by monoamine oxidase inhibition produced a total suppression of raphe cell activity in vitro. Similarly, increasing the concentration of serotonin in the tissue slice by adding serotonin directly to the incubation medium resulted in a profound, though transitory, depression of RD neuron activity. This depressant effect of serotonin was rapidly reversible upon drug wash-out. Serotonin receptor blockers, methiothepin, cyproheptadine and methysergide produced no significant change in RD cell activity. The 5HT reuptake blocker, fluoxetine, produced a total suppression of RD neuron activity in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)