In previous studies, we showed that localized perfusion of the SCN region with serotonin (5-HT) or the non-selective serotonergic, quipazine, using the microdialysis technique significantly reduced the extracellular concentration of the excitatory amino acid (EAA), glutamate. The present investigation was undertaken to extend these findings by characterizing the effects of various classes of 5-HT receptor ligands on the extracellular glutamate concentration in the SCN. Localized SCN application or i.p. injection of the 5-HT1A receptor agonist, 8-OH-DPAT, during the dark phase (6 h after lights-off) significantly reduced the extracellular glutamate concentration in the SCN region from baseline levels (38.7 +/- 8.7 and 53.4 +/- 11.2%, respectively, of pretreatment values; P < 0.05). The effect of systemically applied 8-OH-DPAT was abolished by i.p. injection of the 5-HT1A receptor antagonist, NAN-190, administered 20 min before the 8-OH-DPAT. Localized perfusion of the SCN with the 5-HT1B receptor agonist, TMFPP, also reduced extracellular glutamate but to a lesser degree than 8-OH-DPAT (80.1 +/- 3.9% of pretreatment levels; P < 0.05). This effect was prevented by i.p. injection of the non-selective 5-HT receptor antagonist, metergoline 20 min before TFMPP perfusion. Localized perfusion of the SCN region with the 5-HT2 and 5-HT3 receptor agonists, alpha-methyl 5-HT and 1-phenylbiguanide, respectively, had little effect on extracellular glutamate (both P > 0.1 vs. baseline). Systemic treatment with NAN-190 alone had little effect on extracellular glutamate, however, similar treatments with metergoline or the 5-HT2 receptor antagonist, ritanserin, induced significant increases extracellular glutamate levels.(ABSTRACT TRUNCATED AT 250 WORDS)