Improving effect of acetylcholine receptor agonists on a deficit of 2-deoxyglucose uptake in cerebral cortical and hippocampal slices in aged and AF64A-treated rats.
The aim of the present study was to determine whether the facilitation of 2-deoxyglucose (2-DG) uptake in the cerebral and hippocampal slices by nicotinic and muscarinic receptor agonists is compromised in the aged rat brain. For this, the effects of the nicotinic receptor agonist nicotine, the muscarinic receptor agonists oxotremorine and McN-A-343, and the ACh esterase inhibitors physostigmine and NK247 on 2-DG uptake in the brain slices of young (2-month-old) and aged (24-26-month-old) rats were tested. The decrements of 2-DG uptake in the cortical slices of aged rats were significantly attenuated by treatment with oxotremorine, nicotine and amiridine. In contrast, the metabolic responsivity of hippocampal slices to these drugs was reduced. To assess whether age-related changes in 2-DG uptake may be due to deficits in cholinergic function, we tested these drugs on the decrements of 2-DG uptake in ethylcholine aziridinium (a neurotoxic analog of choline) injected rats. The reductions of 2-DG uptake by injection of ethylcholine aziridinium was attenuated by oxotremorine but not by physostigmine. The present results reveal that metabolic decrements in the cerebral cortex from aged or ethylcholine aziridinium-injected rats were attenuated by muscarinic and nicotinic receptor agonists, suggesting that the muscarinic and nicotinic receptor mechanism in the cerebral cortex may be involved in cholinergic drug-induced functional recovery in aged rats.
Shibata
S
S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Kodama
K
K
Koga
Y
Y
Ueki
S
S
Watanabe
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001388:Aziridines / Q000008:administration & dosage / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D002794:Choline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D008297:Male; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology*; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000502:physiology*; D012601:Scopolamine / Q000494:pharmacology
D001388:Aziridines; D009466:Neuromuscular Blocking Agents; D010277:Parasympathomimetics; D011950:Receptors, Cholinergic; D010095:Oxotremorine; D009538:Nicotine; D003847:Deoxyglucose; D010830:Physostigmine; C044894:ethylcholine aziridinium; D012601:Scopolamine; D002794:Choline; D000109:Acetylcholine