title: The sleep inducing brain lipid cis-oleamide (cOA) does not modulate serotonergic transmission in the CA1 pyramidal neurons of the hippocampus in vitro.
abstract: cis-Oleamide (cOA) is a novel sleep inducing brain lipid with an unknown mechanism of action. High affinity interactions with metabotropic 5-HT receptors (2A/C and 1A subtypes) in frog oocytes and expression systems have been reported, but functional in vitro evidence for the modulatory effect is still lacking. Here, we addressed the ability of cOA to modulate 5-HT-induced cellular actions in the CA1 neurons of the rat hippocampal slice.5-HT (0.1-100 microM) concentration dependently reduced the amplitude of the evoked field population spike (fPS), and produced a hyperpolarising shift in the resting membrane potential (Vr) and a drop in input resistance (R in). The effects of a low dose of 5-HT (3.2 microM) on fPS, Vr and R in were reversed by the specific 5-HT(1A)-receptor antagonist WAY 100135 (10 microM). cOA (1 microM) failed to potentiate 5-HT1A receptor mediated effects on fPS, Vr or R in. High doses of 5-HT also recruited both 5-HT2 and 5-HT3 receptors, causing an increase in the rate and amplitude of sIPSCs. cOA (1 microM), in the presence of Y 25130, failed to potentiate the 5-HT2 receptor induced enhancement of sIPSCs. In summary, cis-oleamide failed to modulate metabotropic responses to exogenous 5-HT in this microelectrode study at concentrations well in excess of those reported to modulate 5-HT1A and 5-HT2A/C systems in earlier studies.
authors.affiliation: Sunderland Pharmacy School, School of Health, Social and Natural Sciences, University of Sunderland, Chester Road Campus, Wharncliffe Street, Sunderland, SR1 3SD, UK.
authors.forename: Antonios
authors.initials: A
authors.lastname: Dougalis
authors.forename: George
authors.initials: G
authors.lastname: Lees
authors.forename: C Robin
authors.initials: CR
authors.lastname: Ganellin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects / Q000528:radiation effects; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009829:Oleic Acids / Q000378:metabolism* / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D017966:Pyramidal Cells / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D012890:Sleep / Q000502:physiology*
chemical_list: D009829:Oleic Acids; D012702:Serotonin Antagonists; D012701:Serotonin; C029407:oleylamide