Ramelteon Ameliorates Isoflurane-Induced Hyperactivity and Social-Recognition Impairment in Aged Mice

Area of Science:

• Neuroscience
• Pharmacology
• Gerontology

Background:

• Postoperative delirium (POD) is a concern, with ramelteon (melatonin receptor agonist) showing potential but controversial efficacy.
• Mechanisms of ramelteon's effects on POD and related behavioral/molecular changes are not well understood.
• Few animal studies have investigated ramelteon's impact on postoperative neurobehavioral and molecular alterations.

Purpose of the Study:

• To investigate ramelteon's effects on postoperative behavioral changes.
• To analyze ramelteon's impact on neuroinflammation and molecular changes post-surgery.
• To clarify ramelteon's potential role in mitigating anesthesia-induced cognitive and behavioral deficits.

Main Methods:

• Aged mice received ramelteon (0.03 or 0.3 mg/kg) or placebo daily for 7 days before abdominal surgery under isoflurane anesthesia.
• Postoperative locomotor activity, social recognition, working memory, and novel-object recognition were assessed.
• Cytokine levels (interleukin-1β) and microglial activation in the prefrontal cortex and hippocampus were analyzed post-surgery.

Main Results:

• Isoflurane anesthesia induced hyperactivity and impaired social recognition but did not affect working memory or novel-object recognition.
• Ramelteon (0.3 mg/kg) attenuated postoperative hyperactivity and preserved social recognition.
• Ramelteon significantly reduced interleukin-1β elevation in the prefrontal cortex post-surgery.

Conclusions:

• Anesthesia and surgery caused significant behavioral changes, including hyperactivity and social recognition deficits.
• Ramelteon demonstrated potential in alleviating these specific postoperative behavioral and neuroinflammatory changes.
• Ramelteon may be a promising therapeutic agent for preventing certain neurobehavioral alterations following surgical procedures.