8-OH-DPAT attenuates the dexfenfluramine-induced increase in extracellular serotonin: an in vivo dialysis study.

Rats with frontocortical microdialysis probes were treated with dexfenfluramine or dexfenfluramine with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) pretreatment. Dexfenfluramine (10 mg/kg i.p.) increased extracellular serotonin (5-hydroxytryptamine, 5-HT) (calculated area under the curve (AUC) for the 0 to 105-min period after dexfenfluramine treatment = 8.22 +/- 2.66 pmol 5-HT). Systemic (0.025 mg/kg i.p.) or local (0.01 microM into the dorsal raphe nucleus) 8-OH-DPAT pretreatement decreased the dexfenfluramine response (AUC: 1.03 +/- 0.07 and 0.44 +/- 0.04 pmol 5-HT, respectively). This result might be explained by the decrease in 5-HT neuronal discharge caused by somatodendritic 5-HT1A autoreceptor activation, and suggests that the 5-HT releasing effect of dexfenfluramine in vivo depends on nerve terminal depolarization.