CHRONIC TREATMENT WITH FLUVOXAMINE BY OSMOTIC MINIPUMPS FAILS TO INDUCE PERSISTENT FUNCTIONAL-CHANGES IN CENTRAL 5-HT1A AND 5-HT1B RECEPTORS, AS MEASURED BY IN-VIVO MICRODIALYSIS IN DORSAL HIPPOCAMPUS OF CONSCIOUS RATS

This study investigated the alterations of the 5-HT1A and 5-HT1B autor eceptor function following chronic treatment with fluvoxamine using os motic minipumps. The 5-HT1A and 5-HT1B autoreceptor function were stud ied using microdialysis in the dorsal hippocampus. The effect of the 5 -HT1A receptor agonist 8-OH-DPAT (0.3 mg/kg, SC) and the 5-HT1B recept or agonist RU-24969 (100 nM through the dialysis probe for 30 min) on 5-HT release was compared with rats chronically treated with saline. 8 -OH-DPAT decreased 5-HT release to 55% and 60% of baseline, while RU-2 4969 decreased 5-HT release to 66% and 70% of baseline value in the sa line and fluvoxamine group, respectively. In both cases, differences b etween the saline and fluvoxamine groups were not statistically signif icant. Plasma levels of fluvoxamine after 21 days of treatment ranged from 3 to 5 ng/ml. Fluvoxamine concentration in rat brain during treat ment was estimated between 100 and 200 nM, which approximates to the I C50 value of fluvoxamine on the 5-HT transporter in synaptosomes and i s 50 times higher than the K-d value for the 5-HT reuptake site. In co nclusion, no evidence was found for changes in 5-HT1A,B receptor funct ion using 8-OH-DPAT and RU-24969 as probes after continuous treatment with fluvoxamine by means of osmotic minipumps.