Extracellular 5 hydroxytryptamine in many rat brain sites is increased after endemic administrationof a reuptake inhibitor. But, the escalation in extracellular5 HT after reuptakeblockade is restrained by the resultant inhibition of 5 HT neuronalactivity and activation of somatodendritic and nerve terminal autoreceptors. Accordingly, autoreceptor antagonists increased the increase Factor Xa in forebrain 5 HT made by reuptake inhibitors. It has been noted as a result of autoreceptor desensitization that during prolonged therapy with antidepressant drugs, 5 HT neuronal activitymay gradually recover. As an example, after repeated administration of citalopram, a particular 5 HT reuptake inhibitor, 5 HT neuronal discharge returned towards normal and autoreceptor sensitivitywas decreased. Nevertheless, there were no changes in baseline discharge supplier Myricetin of 5 HT nerves or sensitivity to direct operating 5 HTIA receptor agonists after repeated administration of the 5 HT reuptake inhibitor cericlamine. Also, a 5 HTIA autoreceptor Urogenital pelvic malignancy antagonist, UH 301, however produced significant increases in 5 HT neuronal discharge in rats treated for just two weeks with the reuptake inhibitor citalopram. Many in vivo microdialysis reports support the hypothesis that prolonged antidepressant treatment results in decreased autoreceptor awareness and increases reuptake blocker mediated increases in extracellular 5 HT. However, other studies using similar techniques do not support this conclusion. More over, the enhancement of citalopram inducedincreases in extracellular 5 HT created by the 5 HT1receptor antagonist UH 301 was still evident after prolonged citalopram treatment. These sporadic resultsmay supplier Gossypol reflect the usage of differentreuptake inhibitors and dosing standards in these tests. Regional differences in antidepressant effects on extracellular 5 HT is another possible explanation for these inconsistent results. Systemic administration of reuptake inhibitors produced minimum increase in frontal cortex 5 HT, suggesting that release here might be more closely controlled than in other forebrain websites. This may depend on higher density or sensitivity of 5 HT autoreceptors in the DRN, which is really a major supply of 5 HT terminals in the FCX. In line with this possibi, lity, chronic fluvoxamine enhanced reuptake blockerinduced increases in FCX5 HT, but not in the dorsal hippocampus, which is predominantly innervated by 5 HT predictions from the median raphe nucleus. In contrast,chronic citalopram administration slightly increased the escalation in DH 5 HT elicitedby serious nearby citalopraminfusion,but had no significant effect in FCX.