British journal of anaesthesia · 2025
Drug-specific recovery of long-term memory and visual discrimination after anaesthetic-induced unconsciousness in rats.
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Obert David P, Park Gwi H, Vincent Kathleen F, Solt Ken
Аннотация
BACKGROUND: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.