5-HT3-LIKE RECEPTORS IN THE RAT MEDIAL PREFRONTAL CORTEX - FURTHER PHARMACOLOGICAL CHARACTERIZATION

The aim of the study was to further characterize the pharmacological p roperties of 5-hydroxytryptamine (5-HT)(3)-like receptors in the rat m edial prefrontal cortex (mPFC) using combinations of biochemical and e lectrophysiological approaches. Phenylbiguanide (PEG) and three chlori nated derivatives, ortho-chloro-PBG (oCPBG), meta-chloro-PBG (mCPBG) a nd para-chloro-PBG (pCPBG), dose-dependently stimulated phosphoionosit ide (PI) turnover in fronto-cingulate cortical slices. All three chlor o-isomers of PBG were equipotent in stimulating PI turnover. SR 57227A ((4-amino)-(6-chloro-2-pyridyl) L-piperidine hydrochloride, a novel c ompound with high affinity and selectivity for peripheral and central 5-HT3 receptors) dose-dependently stimulated PI turnover in fronto-cin gulate cortical slices. The rank order of potency of all the 5-HT3 rec eptor agonists tested in the PI assay as compared to 5-HT was: 5-HT > 2-Me-5-HT > SR57227A > PBG = mCPBG = oCPBG = mCPBG. 5-HT and 5-HT rece ptor agonists depressed the firing rate of both spontaneously active a nd glutamate-activated quiescent mPFC cells in a current (dose)-depend ent fashion. The rank order of effectiveness of these compounds was: 5 -HT > SR57227A = 2-Me-5-HT = mCPBG = oCPBG = pCPBG = PBG. Unlike its a ction on the 5-HT3 receptors in the periphery or cultured cell Lines, D-tubocurarine chloride appears to be non-specific in blocking the dep ressant action of 2-Me-5-HT, gamma-aminobutyric acid and dopamine. Our results combined support the view that the pharmacological properties of 5-HT3-like receptors in the mPFC are not identical to those locate d in peripheral tissues and in cultured cell lines.