Electrical stimulation of the dorsal and median raphe nuclei increases extracellular noradrenaline in rat hippocampus: Evidence for a 5-HT-independent mechanism.

Recent studies have used raphe stimulation combined with in vivo measurements of extracellular dopamine to investigate interactions between the 5-hydroxytryptamine (5-HT) and dopamine systems. Here we have tested whether the same approach can be used to investigate interactions between the 5-HT and noradrenaline systems. Electrical stimulation of the dorsal raphe nucleus (DRN) or median raphe nucleus (MRN) was performed in anaesthetised rats implanted with microdialysis probes in the hippocampus and locus coeruleus (LC). DRN stimulation (3, 5 and 10 Hz) evoked a frequency-dependent increase in extracellular noradrenaline in the hippocampus. MRN stimulation had a similar effect. Both DRN and MRN stimulations enhanced extracellular 5-HT levels in the LC and previous studies have demonstrated that extracellular 5-HT also increases in the hippocampus. However, the increase in hippocampal noradrenaline evoked by DRN stimulation was not altered by 5-HT neuronal lesions, which reduced 5-HT metabolite levels by 90%. In conclusion, electrical stimulation of the midbrain raphe increases extracellular noradrenaline in the hippocampus, however, experiments in 5-HT-lesioned animals suggest that this response is not mediated by 5-HT. Although raphe stimulation may be useful to investigate interactions between 5-HT and dopamine, our data indicate that the same approach may not be feasible for 5-HT and noradrenaline