| 18081887 |
Fiske E, Portas CM, Gronli J, Sorensen E, Bjorvatn B, Bjorkum AA, Ursin R: Increased extracellular 5-HT but no change in sleep after perfusion of a 5-HT1A antagonist into the dorsal raphe nucleus of rats. Acta Physiol. 2008 May;193(1):89-97. Epub 2007 Dec 14.
AIM: The 5-HT (1A) receptor antagonist 4-Iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl] ethyl]-N-2-pyridinyl-benzamid e 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. |
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