The effect of GABA(A) antagonist bicuculline on dorsal raphe nucleus and frontal cortex extracellular serotonin: a window on SWS and REM sleep modulation.

We investigated the effects of the perfusion of gamma-aminobutyric acid(A) antagonist bicuculline in the dorsal raphe nucleus, on brain 5-hydroxytryptamine level and on sleep. Perfusion of 25 and 50 microM bicuculline into the dorsal raphe nucleus dose-dependently increased dorsal raphe nucleus 5-hydroxytryptamine level during sleep and wakefulness. Frontal cortex 5-hydroxytryptamine level was not affected by either 25 or 50 microM perfusion. 25 microM bicuculline produced only minimal effects on sleep. 50 microM decreased rapid eye movement sleep, slow wave sleep 1 and 2 and increased waking. Sleep changes leveled out towards the end of the bicuculline perfusion despite serotonin levels were still elevated. This suggests that an adaptation mechanism may take place in order to counteract the high serotonergic output, producing uncoupling between serotonin level and behavioural state. The results support the notion that gamma-aminobutyric acid is a strong modulator of dorsal raphe nucleus serotonergic neurons, and that this modulation is important in the regulation of slow wave sleep, rapid eye movement sleep and waking.