Differential actions of ketamine on CA3-prelimbic and CA3-infralimbic connection responsivity depend on prior exposure to stress

Abstract

The present study explored the behavioral stressing action of a 15-min forced swim test (FST) session, changes in CA3-medial prefrontal cortex (mPFC) connection responsivity, and whether ketamine reverses such changes. Two groups of male Wistar rats were subjected to a 15-min FST session. Sixty minutes later, they were injected with either saline (stress [STR] SAL group) or ketamine (STR KET group). Twenty-four hours later, these two groups underwent an open field test (OFT) and a 5-min FST session. The other two groups received similar treatments (SAL group and KET group) without being subjected to the FST. In all four groups, single-unit extracellular recordings from the prelimbic (PL) and infralimbic (IL) regions of the mPFC were obtained while the CA3 hippocampal region was stimulated. Ketamine decreased the time spent immobile in the FST without altering behavior in the OFT. In the SAL group, CA3 stimulation produced an inhibitory response in the PL but a strong excitatory response in the IL. In the KET group, there were no changes in connection responsivity in the CA3-PL connection, but an inhibitory response was observed in the CA3-IL connection. Responsivity of the CA3-PL connection was similar between the STR KET and STR SAL groups. In the SAL group, CA3 stimulation produced an inhibitory response in the IL, which was accentuated in the STR SAL group. In the STR KET group, the inhibitory response was abolished. These findings indicate that the CA3-PL connection is sensitive to stress, independent of drug treatment, whereas the CA3-IL connection is sensitive to ketamine, but its action depends on prior stress exposure.