Introduction: Cardiac arrest survival has improved with advances in resuscitation care, but survivors face impairments from the resulting hypoxic-ischemic brain injury (HIBI). Given the popular clinical use of DA modulators, despite limited understanding of disturbances in DA neurotransmission after HIBI, we characterized striatal DA signaling and behavioral deficits in a rat model of asphyxial cardiac arrest (ACA). Hypothesis: ACA-induced HIBI alters DA neurotransmission linked to behavioral deficits. Methods: Adult male Sprague-Dawley rats (n=41) underwent either Sham procedures (n=10) or 5-min no-flow ACA (n=28) insult. Fast-scan cyclic voltammetry (FSCV) and maximal medial forebrain bundle stimulations (60Hz, 10s) were used to characterize presynaptic DA signaling in dorsal striatum (D-Str). FSCV findings were compared with sensorimotor processing [acoustic startle responses (ASR)], open field exploration (total distance & exploratory zone entries), myoclonus, and anhedonia (sucrose preference testing). Results: ACA increased maximum evoked overflow (fig 1) and several DA release-based kinetic metrics. ACA hindered sensorimotor processing via increased ASR %change, elicited myoclonic responses to auditory stimuli, reduced mobility & exploration, and increased anhedonia. Many behavioral measures correlated with D-Str neurotransmission ( fig 2 ). Conclusions: ACA causes early hypodopaminergia that evolves to a hyperdopaminergic state by 2 weeks that is associated with behavioral dysfunction. Future work should further characterize striatal pathology post-ACA and identify treatments to resolve altered DA signaling and behavioral deficits.
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