Physiological and pharmacological evidence for a serotonergic projection to the hippocampus

Rat hippocampal pyramidal cells were studied for their response to serotonin applied iontophoretically and to stimulation of the midbrain raphe nuclei. Ninety-two percent of the cells studied were inhibited by serotonin. Fourty-eight percent of the cells responded by inhibition to dorsal and median raphe stimulation. The inhibitory response to raphe stimulation was absent when the rats were pretreated with p-chlorophenylalanine (PCPA), a serotonin synthesis inhibitor; PCPA effects were alleviated by 5-HTP or 5-HT administration. The response to raphe stimulation was blocked by emthysergide and cyproheptadine. The responses to raphe stimulation were potentiated by chlorimipramine, a serotonin reuptake blocker. These data satisfy several of the criteria required to identify serotonin as the inhibitory neurotransmitter for the raphe-hippocampal pathway