ONLINE DETECTION OF EXTRACELLULAR LEVELS OF SEROTONIN IN DORSAL RAPHENUCLEUS AND FRONTAL-CORTEX OVER THE SLEEP WAKE CYCLE IN THE FREELY MOVING RAT/

We used in vivo microdialysis coupled with polygraphic recording to mo nitor 5-hydroxytryptamine levels in the dorsal raphe nucleus and front al cortex across waking, slow-wave sleep and rapid eye-movement sleep. Male Sprague-Dawley rats were prepared with electroencephalogram and electromyogram electrodes. Microdialysis probes were placed in dorsal raphe nucleus and/or frontal cortex. Dialysate samples were manually c ollected during polygraphically-defined behavioural states and the lev el of serotonin was assayed by means of microbore high-performance liq uid chromatography separation and electrochemical detection. Samples f rom microdialysis probes histologically localized to the dorsal raphe nucleus and frontal cortex showed different levels of extracellular 5- hydroxytryptamine in waking, slow-wave sleep and rapid eye-movement sl eep. In dorsal raphe nucleus the extracellular level of serotonin was highest in waking, decreased in slow-wave sleep to 69% and in rapid ey e-movement sleep to 39% of waking mean level (waking 3.2+/-0.9; slow-w ave sleep 2.2+/-0.8; rapid eye-movement sleep 1.3+/-0.4 fmol/sample). Mean extracellular levels of serotonin in frontal cortex displayed a s imilar pattern (waking 1.7+/-0.4; slow-wave sleep 1.0+/-0.3; rapid eye -movement 0.5+/-0.05 fmol/sample). In frontal cortex, rapid eye-moveme nt sleep samples were only obtained in three animals. Our findings are consistent with previous results in cats, and suggest that in rats al so, extracellular 5-hydroxytryptamine levels in dorsal raphe nucleus a nd frontal cortex across the sleep/wake cycle might reflect serotonerg ic neuronal activity. The findings stress the importance of controllin g for behavioural state when investigating neurochemical correlates of serotonergic function. (C) 1998 IBRO. Published by Elsevier Science L td.