Serotonin (5-HT)2C receptors tonically inhibit dopamine (DA) and noradrenaline (NA), but not 5-HT, release in the frontal cortex in vivo.
The novel, preferential 5-HT2C receptor agonist, Ro 60-0175 ((S)-2-(6-chloro-5-fluoroindol-1-yl)-1-methylethylamine) (2.5 mg,kg, s.c.), markedly suppressed dialysate levels of dopamine (DA) and noradrenaline (NA) levels in the frontal cortex of freely-moving rats without affecting levels of 5-HT. In contrast, the novel and selective 5-HT2C receptor antagonist, SB-242084 (6-chloro-5-methyl-1-[6-(2-methylpyridin-3-yloxy) pyridin-3-yl carbamoyl] indoline) (10.0 mg/kg, i.p.), markedly increased dialysate levels of DA and NA without modifying those of 5-HT. These data suggest that 5-HT2C receptors exert a tonic, inhibitory influence upon frontocortical dopaminergic and adrenergic, but not serotonergic, transmission.
Institut de Recherches Servier, Psychopharmacology Department, Paris, France.
M J
MJ
Millan
A
A
Dekeyne
A
A
Gobert
D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D005021:Ethylamines / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D005021:Ethylamines; D007211:Indoles; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; C103848:Ro 60-0175; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine