Dorsal hippocampal CA3-CA1 long-term plasticity and the effect of aerobic exercise in anaesthetised and awake sub-chronic phencyclidine rat model for schizophrenia

Background: Hippocampal memory deficit is an important symptom in patients with schizophrenia that responds poorly to antipsychotic treatment. Here, we investigated deficits in hippocampal long-term potentiation/depotentiation changes in the sub-chronic phencyclidine (scPCP) rat model for schizophrenia and how chronic exercise as a non-pharmacological treatment may produce hippocampal synaptic and cognitive improvements.Methods: 60 Female Lister Hooded rats (50 for acute recording and 10 for chronic recording) were dosed with either saline or PCP (2 mg/kg, i.p.) twice daily for seven days followed by a 7-day washout. Running wheels were provided for aerobic exercise for 1 hour daily over 30 days. Synaptic plasticity in the dorsal hippocampus was then assessed in these groups via in vivo electrophysiology when either under urethane anaesthesia (30% w.v.; 1.4g/kg i.p.) or awake-free-moving. The hippocampal CA1 Schaffer- evoked field excitatory postsynaptic potential (fEPSP) was analysed to measure short and long-term synaptic plasticity. Data were analysed with Student t-test and mixed-effect three-way ANOVA.Results: The scPCP group responded to exercise with increased long-term potentiation induction after high-frequency stimulation, increased resistance to depotentiation after low-frequency stimulation, and improved baseline short-term plasticity. In conclusion, chronic exercise appears to improve hippocampal synaptic function in the scPCP rat model. The result of ongoing awake recording will be included on the poster.