Age-related modifications of effects of ketamine and propofol on rat hippocampal acetylcholine release studied by in vivo brain microdialysis

Background: We sometimes encounter impairment of learning and memory after general anesthesia in elderly patients. The aim of this study was to examin e age-related modifications of the effects of ketamine and propofol on rat hippocampal acetylcholine (ACh) release because hippocampal cholinergic neu rons are supposed to be involved in learning and memory. Methods: The experiments were performed on male Wistar young rats (2 months old) and old rats (18 months old), using in vivo brain microdialysis techn ique under freely moving condition. After initial sampling of three collect ions, test drugs were administered. The ACh release was determined by the H PLC-ECD method. Results: In old rats, the hippocampal basal ACh release was significantly l ower than in young rats. Ketamine (25 and 50 mg kg(-1) i.p.) increased and propofol (25 and 50 mg kg(-1) i.p.) decreased the hippocampal ACh release i n both young and old rats. Furthermore, ketamine 50 mg kg(-1) i,p. (anesthe tic dose) produced facilitatory effects on the hippocampal ACh release in y oung rats (193% of the basal release), while in old rats the same dose of k etamine i.p. produced more pronounced facilitatory effects on the hippocamp al ACh release (317% of the basal release). On the other hand, propofol 50 mg kg(-1) i.p. (anesthetic dose) produced inhibitory effects on the hippoca mpal ACh release in young rats (56% of control) and in old rats (77% of con trol). Although the maximal inhibitory peak effects of propofol 50 mg kg(-1 ) i.p. did not differ significantly between young rats and old rats, decrea se of the hippocampal ACh release in old rats persisted longer than in youn g rats. Conclusion: Ketamine produced more pronounced facilitatory effects on the h ippocampal ACh release in old rats, as compared with young rats. On the oth er hand, propofol has inhibitory effects on the hippocampal ACh release in young and old rats. The aging process may suppress the ability to recover f rom the inhibitory anesthetic state induced by propofol.