Acute dissociation of coping and anhedonia-like behavior following focal medial prefrontal ischemia in rats

Abstract: CONTEXT: Cognitive and emotional alterations are common but underrecognized during the acute phase after ischemic stroke. Although the medial prefrontal cortex (mPFC) plays a central role in emotional regulation and executive control, the early behavioral consequences of focal ischemic damage to this region remain poorly characterized. AIMS: The aim of the study was to investigate acute emotional, cognitive, and motor outcomes following focal ischemic damage to the mPFC. SETTINGS AND DESIGN: Experimental animal study using a focal endothelin-1 (ET-1)–induced ischemia model targeting the mPFC in male and female rats, assessed during the acute phase. MATERIALS AND METHODS: Emotional behavior was assessed during the first 4 days after stroke using the elevated plus maze (EPM), forced swim test (FST), and sucrose preference test (SPT). Cognitive performance was evaluated using the four-choice odor discrimination task. Motor function was assessed using the beam-walking test and the Rogers functional scale. STATISTICAL ANALYSES USED: Behavioral outcomes were analyzed using two-way analysis of variance or generalized linear models, as appropriate, with lesion (stroke vs. sham) and sex as between-subject factors. RESULTS: Focal mPFC ischemia induced anxiety-like behavior in the EPM and promoted a shift toward passive coping in the FST. No evidence of anhedonia-like behavior was observed in the SPT, and cognitive and motor performance remained intact. No significant Sex x Lesion interactions were identified. CONCLUSIONS: Focal ischemic damage to the mPFC selectively disrupts emotional regulation during the acute phase, revealing an early dissociation between stress-related behavioral responses and reward processing. These findings support the ET-1 mPFC model for studying post-stroke emotional symptoms.