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


CONCLUSIONS
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.
Fiske
E
E
Department of Biomedicine, University of Bergen, Bergen, Norway. eldbjorg.fiske@biomed.uib.no
Portas
C M
CM
Grønli
J
J
Sørensen
E
E
Bjorvatn
B
B
Bjørkum
A A
AA
Ursin
R
R
D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D017551:Microdialysis / Q000379:methods; D010879:Piperazines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000096:biosynthesis* / Q000502:physiology; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology*; D012894:Sleep Stages / Q000187:drug effects* / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
D000631:Aminopyridines; D010879:Piperazines; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; C087205:4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine; D012701:Serotonin