The sleep inducing brain lipid cis-oleamide (cOA) does not modulate serotonergic transmission in the CA1 pyramidal neurons of the hippocampus in vitro

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 muM) concentration dependently reduced the amplitude of the evoked field population spike (fPS), and produced a hyperpolarising shift in the resting membrane potential (V-r) and a drop in input resistance (R-in). The effects of a low dose of 5HT (3.2 muM) on fPS, V-r and R-in were reversed by the specific 5-HT1A-receptor antagonist WAY 100135 (10 muM). cOA (1 muM) failed to potentiate 5-HT1A receptor mediated effects on fPS, V-r 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 muM), in the presence of Y 25130, failed to potentiate the 5-HT, 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. (C) 2003 Elsevier Ltd. All rights reserved.