Role of dorsal raphe neurons in paradoxical sleep generation in the cat: no evidence for a serotonergic mechanism

Using in vivo microdialysis either alone or in combination with extracellular unit recordings, we have examined the effect of serotonergic and nonserotonergic drugs applied to the dorsal raphe nucleus (DRN) on behavioural states in the cat. We found that 8-hydroxy-2-(n-dipropylamino)tetralin hydrobromide (8-OH-DPAT), a selective 5-HT1A receptor agonist, induced a dose-dependent increase in wakefulness (W) and decrease in deep slow-wave sleep (SWS), but had no significant effect on the generation of paradoxical sleep (PS) at concentrations of 5-500 muM At the highest concentration tested, however, PS occurred directly after W, as in narcolepsy. N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-cyclohexanecarboxamide maleate (WAY-100635), a selective 5-HT1A receptor antagonist, had no effect on overall behavioural states at concentrations of 50 or 500 muM. Muscimol, a potent GABA(A) receptor agonist, had little or no effect at concentrations of 10, 50 or 100 muM, but concentrations of 500 or 1000 muM caused a pronounced increase in W and decrease in SWS without inducing any changes in the amount of PS, although PS episodes occurred as in narcolepsy. Bicuculline, a GABA(A) receptor antagonist, or kainate, an excitatory amino acid agonist, produced a dose-dependent increase in W and decrease in deep SWS and PS. Extracellular unit recordings combined with microdialysis infusion into the DRN demonstrated that only high concentrations of 8-OH-DPAT or muscimol significantly affect a large population of DRN neurons. Taken together, these findings indicate that DRN serotonergic activity does not play any crucial role in PS generation, but is involved in the regulation of W and SWS as well as in narcolepsy.