Effects of 4-weeks of treatment with lithium and olanzapine on long-term potentiation in hippocampal area CA1

Neuroplastic theories propose that lithium has robust neuroprotective and neurotrophic actions leading to the up-regulation of synaptic plasticity, and this action may be associated with the efficacy of lithium in the treatment of bipolar disorder. Olanzapine, an atypical antipsychotic drug, is efficacious in the treatment of bipolar disorder. It has been suggested that olanzapine may also up-regulate synaptic plasticity by its neuroprotective and neurotrophic actions, and this action may be related to antipsychotic and anti-manic effects of the drug. However, few studies have directly examined whether these drugs alter synaptic plasticity. In the present study, to examine the effects of lithium and olanzapine on synaptic plasticity, we examined the effects of chronic treatment with lithium and olanzapine on long-term potentiation (LTP) and input and output (I/O) responses of field excitatory postsynaptic potentials (fEPSP) of CA1 pyramidal cells in hippocampal slices prepared from rats administered the drugs for 4 weeks. Our results show that 4 weeks of lithium treatment magnified LTP of CA1 pyramidal cells. However, the same treatment with olanzapine did not magnify LTP of CA1 pyramidal cells. Four weeks of treatment with lithium did not alter I/O responses of CA1 pyramidal cells. However, the same treatment with olanzapine increased I/O responses of CA1 pyramidal cells. The results suggest that lithium up-regulates synaptic plasticity in the hippocampus, and olanzapine increases synaptic transmission without apparent changes in LTP in the hippocampus.