Drug-specific recovery of long-term memory and visual discrimination after anaesthetic-induced unconsciousness in rats.

Abstract

Perioperative neurocognitive disorders represent a growing public health concern. To improve the translatability of preclinical findings, it is important to use similar research methods across species. In this study, we used a touchscreen-based cognitive testing system to train rats on the paired-associate learning (PAL) task, which assesses long-term visuospatial associative memory. The goal was to capture the time course of cognitive recovery after receiving mechanistically distinct anaesthetic drugs. Adult Sprague-Dawley rats (eight males, eight females) were trained on the interference PAL (iPAL) task. After reaching proficiency, loss of righting was induced with propofol (10 mg kg^-1 i.v.), sevoflurane (20 min at 3 vol%), dexmedetomidine (20 μg kg^-1 i.v.), ketamine (50 mg kg^-1 i.v.), or fentanyl (50 μg kg^-1 i.v.). We evaluated time to return of righting reflex (RORR) and time to cognitive recovery, defined as 4/5 correct on the first try. Data are presented as median (first quartile-third quartile). The number of sessions to achieve proficiency was 51 (45-57). Latency to RORR was 11.5 (7.2-12.7) min after propofol, 4.9 (3.6-7.9) min after sevoflurane, 63.7 (48.6-72.0) min after dexmedetomidine, 31.6 (27.0-35.9) min after fentanyl, and 28.1 (19.3-32.3) min after ketamine. Compared with baseline, time to reach 4/5 correct was prolonged after all drugs (all P<0.001). Although animals recovered cognition within 60 min after RORR after propofol and sevoflurane, it took 2-3 h after ketamine, dexmedetomidine, and fentanyl. All animals returned to baseline performance within 24 h. We found distinct recovery profiles of neurocognitive function after the different drugs, consistent with their distinct pharmacologic properties. The iPAL touchscreen-based cognitive testing system allows evaluation of long-term visuospatial memory after drug-induced unconsciousness, providing a robust, translatable method for future studies of perioperative neurocognitive disorders.