High-dose fluoxetine improved long-term potentiation of the hippocampal dentate gyrus in male rats

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.

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.

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.

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.