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.
Gardier
A M
AM
Faculté de Pharmacie, Laboratoire de Pharmacologie JE 92-372, Chatenay-Malabry, France.
Trillat
A C
AC
Malagié
I
I
Jacquot
C
C
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005277:Fenfluramine / Q000494:pharmacology*; D005625:Frontal Lobe / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*
D005277:Fenfluramine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin