Inhibition of amino acid release by 5-HT1B receptor agonist in the rat prefrontal cortex

In vivo microdialysis in conscious rats was used to evaluate the effect of 5-HT1A agonist (+/-)-8-hydroxy-2-(n-dipropylamino)tetralin (8-OH-DPAT), 5-HT2A/2C agonist (+/-)- 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and 5-HT1B receptor agonist 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo-[3,2-b]pyrid-5-one (CP 93129) on the veratridine-evoked glutamate (Glu) and aspartate (Asp) release in the rat prefrontal cortex. CP 93129 at concentrations between 50-500 microM significantly reduced Glu and Asp release. The effect of CP 93129 was attenuated by intraperitoneal (ip) administration of the selective 5-HT1B receptor antagonist N-[3-[3-(dimethylamino)ethoxy]-4-methoxyphenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-[ 1, 1'-biphenyl]-4-carboxamide (SB 216641) at a dose of 2 mg/kg. Neither DOI (100 microM) nor 8-OH-DPAT given locally at concentration of 100 microM or peripherally at doses of 0.1 and 1 mg/kg ip, influenced stimulated Glu and Asp release. We suggest that cortical glutamatergic neurons possess 5-HT1B heteroceptors and their activation may be responsible for the inhibitory effect of 5-HT on Glu and Asp release.