High-Dose Fluoxetine Improved Long-Term Potentiation of the Hippocampal Dentate Gyrus in Male Rats

Introduction: paradoxical data have been reported regarding the effects of fluoxetine on different types of learning and memory. hippocampus-dependent memory is mediated by long-term potentiation (ltp). here, we evaluated the effects of acute administration of fluoxetine on ltp induction in the hippocampal dentate gyrus of intact rats. methods: eighteen rats were divided into three groups: the control group received saline 15min before high-frequency stimulation (hfs) and the fluoxetine groups were treated with fluoxetine (2 or 10mg/kg), 15min before hfs. the rats were anesthetized with urethane and put in a stereotaxic system for surgery, electrode implantation and field recording. after ensuring a steady-state baseline response, a single intraperitoneal injection of saline or fluoxetine (2 or 10mg/kg) was done. next, population spike amplitude, excitatory postsynaptic potential (epsp) slope, and paired-pulse stimuli (to determine recurrent inhibitory interneuron) were measured in the hippocampal dentate gyrus in three groups. results: the results showed that population spike amplitude markedly increased in the fluoxetine (2 and 10mg/kg) group than in the saline group. also, epsp slope induction in the fluoxetine (10mg/kg) group showed an increase, 60min after hfs compared with the control group. fluoxetine did not significantly affect recurrent inhibition. conclusion: these results indicated that the acute administration of high-dose fluoxetine (10mg/kg) can induce ltp. thus, fluoxetine can be considered as a memory enhancer in intact rats.