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This study investigated the alterations of the 5-HT1A and 5-HT1B autoreceptor function following chronic treatment with fluvoxamine using osmotic minipumps. The 5-HT1A and 5-HT1B autoreceptor function were studied 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 receptor 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-24969 decreased 5-HT release to 66% and 70% of baseline value in the saline and fluvoxamine group, respectively. In both cases, differences between the saline and fluvoxamine groups were not statistically significant. Plasma levels of fluvoxamine after 21 days of treatment ranged from 3 to 5 ng/ml. Fluvoxamine concentration in rat brain during treatment was estimated between 100 and 200 nM, which approximates to the IC50 value of fluvoxamine on the 5-HT transporter in synaptosomes and is 50 times higher than the Kd value for the 5-HT reuptake site. In conclusion, no evidence was found for changes in 5-HT1A,B receptor function using 8-OH-DPAT and RU-24969 as probes after continuous treatment with fluvoxamine by means of osmotic minipumps.

Deep brain stimulation (DBS) of the nucleus accumbens (NAc)is effective in treatment-refractory obsessive-compulsive disorder and major depressive disorder. However, little is known about the neurobiological mechanisms underlying the rapid and effective changes of DBS. One of the hypotheses is that DBS modulates activity of monoamine neurotransmitters. In this study, we evaluated the effects of DBS in the NAc core on the extracellular concentration of monoaminergic neurotransmitters in the medial (mPFC) and orbital prefrontal cortex (OFC). Freely moving rats were bilaterally stimulated in the NAc core for 2 h while dopamine, serotonin, and noradrenaline were measured using in vivo microdialysis in the mPFC and the OFC. We report rapid increases in the release of dopamine and serotonin to a maximum of 177% and 127% in the mPFC and an increase up to 171% and 166% for dopamine and noradrenaline in the OFC after onset of stimulation in the NAc core. These results provide further evidence for the distal effects of DBS and corroborate previous clinical and pre-clinical findings of altered neuronal activity in prefrontal areas.