Abstract
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 μM 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-HT 1A autoreceptor activation, and suggests that the 5-HT releasing effect of dexfenfluramine in vivo depends on nerve terminal depolarization.
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