PRESYNAPTIC 5-HT AUTORECEPTORS MODULATE N-METHYL-D-ASPARTATE-EVOKED 5-HYDROXYTRYPTAMINE RELEASE IN THE GUINEA-PIG BRAIN CORTEX

Guinea-pig cerebral cortical slices preincubated with [H-3]S-hydroxytr yptamine ([H-3]5-HT) were superfused with Mg2+-free Krebs' solution. N -Methyl-D-aspartate (NMDA) stimulated tritium overflow in a concentrat ion-dependent manner. The NMDA-evoked overflow was abolished by omissi on of Ca2+ or presence of 1.2 mM Mg2+, but only partly inhibited by te trodotoxin. ?he competitive and noncompetitive NMDA receptor antagonis ts, DL-(E)-2-amino-4-methyl-5-phosphono-3-pentanoic acid (CGP 37849) a nd dizocilpine, respectively, also blocked the stimulatory effect of N MDA. Furthermore, the NMDA-evoked tritium overflow was inhibited by 5- carboxamidotryptamine in a manner susceptible to blockade by methiothe pin, which given alone facilitated overflow. This facilitatory effect was increased in the presence of 6-nitroquipazine, a selective 5-HT re uptake inhibitor. it is concluded that the release of 5-HT in the guin ea-pig cerebral cortex is stimulated via NMDA receptors, which are in part located on the serotoninergic axon terminals, and that the NMDA-e voked 5-HT release is modulated via inhibitory 5-HT autoreceptors.