[Effects of (+/-)-pindolol over increased extracellular 5-HT level induced by fluvoxamine: regional difference in effect among the raphe, dorsal hippocampus and prefrontal cortex as measured by in vivo microdialysis technique].

It is known that the somatodendritic 5-hydroxytryptamine (5-HT)1A autoreceptor works to regulate the action of 5-HT neurons leading to the release of 5-HT. Our present study has addressed the possibility that (+/-)-pindolol, which is a non-selective beta-adrenoceptor antagonist/somatodendritic 5-HT1A autoreceptor antagonist, might have the ability to enhance the level of extracellular 5-HT when used with selective serotonin reuptake inhibitor (SSRI; i.e., fluvoxamine). We have used freely moving rats to measure the extracellular level of 5-HT and dopamine (DA) in the raphe, dorsal hippocampus and prefrontal cortex using an in vivo microdialysis technique. Response power of (+/-)-pindolol (8 mg/kg, i.p.) to the rise in extracellular 5-HT level when used with fluvoxamine (60 mg/kg, i.p.) was significant in the raphe, dorsal hippocampus and prefrontal cortex, while the degree of augmentation was more significant in the prefrontal cortex than in the dorsal hippocampus. The extracellular level of DA when used with (+/-)-pindolol showed a tendency to decrease in the raphe while showing a tendency to increase in the dorsal hippocampus. However, no change occurred in the prefrontal cortex. This indicates that (+/-)-pindolol has the ability to block the somatodendritic 5-HT1A autoreceptors, thereby weakening the fluvoxamine-induced indirect action of the autoreceptors in the raphe. We have obtained positive result for the probability of pindolol augmentation in two regions--dorsal hippocampus and prefrontal cortex. This indicates that augmentation therapy by the combined use of fluvoxamine with 5-HT1A antagonist will be valid and effective.