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 examine age-related modifications of the effects of ketamine and propofol on rat hippocampal acetylcholine (ACh) release because hippocampal cholinergic neurons 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 technique under freely moving condition. After initial sampling of three collections, test drugs were administered. The ACh release was determined by the HPLC-ECD method.


RESULTS
In old rats, the hippocampal basal ACh release was significantly lower 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 in both young and old rats. Furthermore, ketamine 50 mg kg(-1) i.p. (anesthetic dose) produced facilitatory effects on the hippocampal ACh release in young rats (193% of the basal release), while in old rats the same dose of ketamine i.p. produced more pronounced facilitatory effects on the hippocampal 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 hippocampal ACh release in young rats (56% of control) and in old rats (77% of control). Although the maximal inhibitory peak effects of propofol 50 mg kg(-1) i.p. did not differ significantly between young rats and old rats, decrease of the hippocampal ACh release in old rats persisted longer than in young rats.


CONCLUSIONS
Ketamine produced more pronounced facilitatory effects on the hippocampal ACh release in old rats, as compared with young rats. On the other hand, propofol has inhibitory effects on the hippocampal ACh release in young and old rats. The aging process may suppress the ability to recover from the inhibitory anesthetic state induced by propofol.
Wang
Y
Y
Department of Anesthesiology, Yokohama City University School of Medicine, Yokohama, Japan.
Kikuchi
T
T
Sakai
M
M
Wu
J L
JL
Sato
K
K
Okumura
F
F
D000109:Acetylcholine / Q000378:metabolism*; D000367:Age Factors; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000777:Anesthetics; D007649:Ketamine; D000109:Acetylcholine; D015742:Propofol