Chronic Treatment with Fluvoxamine Stimulates Phosphorylation of Ser 473 and Thr 308 of Akt in the Rat Cerebral Cortex

The clinical therapeutic e#ect of most antidepressant drugs only develops after several weeks of administration, but little is known about the intracellular signal transduction in neuron. Here, we examined the e#ect of chronic treatment with fluvoxamine FLV, a selective serotonin reuptake inhibitor SSRI used to treat depression, on the serine-threonine kinase Akt also known as protein kinase B, which plays key roles in various cellular processes including neurotransmitter release, apoptosis and transcription. Male Wistar rats received injections of FLV once daily for 3 weeks, and the protein and phosphorylation levels of Akt in the temporal cortex were determined by immunoblot analysis. The protein expression level of Akt was unchanged from the control after FLV treatment, but phosphorylation of Ser 473 and Thr 308 of Akt was increased compared with the control. The numbers of neurons immunostained for Akt in the somatosensory cortex layer IIIII were similar in the control and FLV groups, but the numbers of phospho Akt-Ser 473 and phospho Akt-Thr 308 -immunoreactive neurons were increased in the FLV group compared with the control. The increase of phospho Akt was localized in the nucleus. The level of brain-derived neurotrophic factor BDNF, an upstream mediator of Akt activation, was also significantly increased in the FLV group. Our results indicate that chronic FLV treatment activates Akt by inducing phosphorylation of Ser 473 and Thr 308 , and the activated Akt is translocated to the nucleus of neurons in the temporal cortex, this may lead to changes of transcriptional regulation.