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.