8-OH-DPAT ATTENUATES THE DEXFENFLURAMINE-INDUCED INCREASE IN EXTRACELLULAR SEROTONIN - AN IN-VIVO DIALYSIS STUDY

Rats with frontocortical microdialysis probes were treated with dexfen fluramine or dexfenfluramine with 8-hydroxy-2-(di-n-propylamino)tetral in (8-OH-DPAT) pretreatement. Dexfenfluramine (10 mg/kg i.p.) increase d extracellular serotonin (5-hydroxytryptamine, 5-HT) (calculated area under the curve (AUC) for the 0 to 105-min period after dexfenflurami ne treatment = 8.22 +/- 2.66 pmol 5-HT). Systemic (0.025 mg/kg i.p.) o r local (0.01 mu M into the dorsal raphe nucleus) 8-OH-DPAT pretreatem ent decreased the dexfenfluramine response (AUC: 1.03 +/- 0.07 and 0.4 4 +/- 0.04 pmol 5-HT, respectively). This result might be explained by the decrease in 5-HT neuronal discharge caused by somatodendritic 5-H T1A autoreceptor activation, and suggests that the 5-HT releasing effe ct of dexfenfluramine in vivo depends on nerve terminal depolarization .