Role of midbrain dopaminergic neurones in post-anaesthetic cognitive recovery in rats

Abstract

Dopaminergic ventral tegmental area (VTA) neurones are critically involved in restoring consciousness after general anaesthesia.1, 2 Whether these circuits contribute to cognitive recovery after emergence is unknown. Previous work using touchscreen-based neurocognitive tasks in rats has shown that after conscious recovery, cognitive recovery trajectories are highly anaesthetic-dependent. Notably, rats have delayed cognitive recovery after dexmedetomidine- and ketamine-induced loss of consciousness (LOC).3 To assess whether circuits known to be involved in re-establishing consciousness can be similarly exploited to hasten cognitive recovery, we used chemogenetic techniques to activate midbrain dopaminergic neurones in rats after dexmedetomidine- and ketamine-induced LOC and measured performance on a sustained attention task. As previous investigations have shown that pharmacologic activation of dopaminergic pathways hastens emergence from dexmedetomidine-, but not ketamine-induced LOC, we hypothesised that activating dopaminergic midbrain neurones would differentially affect cognitive recovery after dexmedetomidine and ketamine exposure.