Depression affects 20% of the general population and is a leading cause of disability worldwide, with one third of patients presenting treatment-resistant depression (TRD). Subanesthetic ketamine is a promising rapid-acting TRD pharmacotherapy, but optimal treatment frequency remains unclear. The present study aims to better understand the effects of an acute (single dose) and chronic (one week daily) 10mg/kg ketamine treatment on hippocampal plasticity, a key mechanism impaired in depression, in a putative TRD model: the Wistar-Kyoto (WKY) rat exposed to chronic mild stress (CMS). Rats were exposed to a 4-week CMS protocol, then subjected to forced swim (FST) and elevated plus maze (EPM) tests. They were then treated with either NaCl, acute or chronic ketamine, and euthanised two hours following the final treatment. Brain slices of dorsal hippocampus were harvested, and synaptic plasticity was studied using field potential recordings of CA1 while stimulating the Schaffer collateral, with either high or low frequency stimulation protocols to trigger LTP and LTD. CMS-exposed rats spent significantly less time exploring the open arms in the EPM and showed higher immobility in the FST versus non-stressed controls, presenting an anxiodepressive-like phenotype. Significant LTP and LTD were observed in controls. LTP and LTD were reduced in NaCl-treated CMS animals. Ketamine impacted both plasticities, although this effect was seemingly different whether the treatment was acute or chronic. These results suggest that as CMS negatively impacts hippocampal plasticity in the WKY rat, acute and chronic ketamine treatment appear to modulate this effect in different ways.