Increased extracellular 5-HT but no change in sleep after perfusion of a 5-HT1A antagonist into the dorsal raphe nucleus of rats.

AIM: The 5-HT(1A) receptor antagonist 4-Iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide hydrochloride (p-MPPI) (10 microM) was perfused into the dorsal raphe nucleus (DRN) to study simultaneously the effects of the drug on the DRN and frontal cortex extracellular serotonin (5-hydroxytryptamine, 5-HT) levels and concurring behavioural states. METHODS: Waking, slow wave sleep and rapid eye movement sleep were determined by polygraphic recordings during microdialysis perfusion and extracellular sample collection. The samples were analysed by microbore high-performance liquid chromatography coupled with electrochemical detection for analysis of 5-HT. RESULTS: p-MPPI perfusion into the DRN (n = 6) produced a sixfold 5-HT increase in the DRN during all behavioural states. The increased 5-HT level was most likely related to the blockage of 5-HT(1A) receptors in the DRN by p-MPPI. No significant effect was seen on sleep. CONCLUSION: Despite the dramatic increase in DRN extracellular 5-HT produced by p-MPPI, only a transient and nonsignificant effect on sleep was recorded. It is suggested that the usual coupling between 5-HT level and behavioural state may be lost when an excessive serotonergic output is pharmacologically achieved.

Effects of sleep deprivation on extracellular serotonin in hippocampus and frontal cortex of the rat.

Sleep deprivation improves the mood of depressed patients, but the exact mechanism behind this effect is unclear. An enhancement of serotonergic neurotransmission has been suggested. In this study, we used in vivo microdialysis to monitor extracellular serotonin in the hippocampus and the frontal cortex of rats during an 8 h sleep deprivation period. These brain regions were selected since both have been implicated in depression. The behavioral state of the animal was continuously monitored by polygraphic recordings during the experiment. Sleep deprivation produced a gradual decline in extracellular serotonin levels, both in the hippocampus and in the frontal cortex. In order to investigate whether the reduction in serotonin was due to other factors than sleep deprivation, i.e. time of day effect, another experiment was performed. Here animals were allowed to sleep during most of the recording period. This experiment showed the expected changes in extracellular serotonin levels: consistently higher levels in the awake, non-sleep deprived animals compared to during sleep, but no time of day effect. The reduction in extracellular serotonin during sleep deprivation may suggest that serotonin does not play a major role in the mood-elevating effect of sleep deprivation. However, since 5-HT levels are strongly behavioral state dependent, by eliminating sleep, there may be a net increase in serotonergic neurotransmission during the sleep deprivation period.