Effects of repeated administration of (-)-nicotine on AF64A-induced learning and memory impairment in rats.
It has been reported that pretreatment with (-)-nicotine prevents glutamate- and amyloid beta protein (Abeta)-induced cytotoxicity in vitro. However, few studies on the neuroprotective effects of (-)-nicotine in vivo have been reported. We examined whether repeated administration of (-)-nicotine exhibits neuroprotective effects in AF64A-treated rats. (-)-Nicotine (0.1 and 0.2 mg/kg, s.c.) was administered once a day for 28 days. On day 14, AF64A (2.5 nmol/side) was injected bilaterally into the hippocampus. Intrahippocampal injection of AF64A showed severe impairment of learning and memory in rats in the water maze and passive avoidance tests. Repeated administration of (-)-nicotine (0.1 and 0.2 mg/kg, s.c.) did not reverse the impairment of memory induced by AF64A in the water maze test. Interestingly, the (-)-nicotine (0.1 and 0.2 mg/kg, s.c.)-treated group showed weak impairment of learning and memory after AF64A treatment compared to the (AF64A + saline)-treated group in the passive avoidance test. These results suggested that (-)-nicotine may have neuroprotective effects against the neurotoxicity induced by AF64A.
Hiramatsu
M
M
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Tenpaku-ku, Nagoya, Japan. mhiramt@ccmfs.meijo-u.ac.jp
Yamatsu
T
T
Kameyama
T
T
Nabeshima
T
T
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000172:deficiency; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001388:Aziridines / Q000494:pharmacology*; D002794:Choline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002795:Choline O-Acetyltransferase / Q000187:drug effects / Q000378:metabolism; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001388:Aziridines; D009466:Neuromuscular Blocking Agents; D018696:Neuroprotective Agents; D009538:Nicotine; C044894:ethylcholine aziridinium; D002795:Choline O-Acetyltransferase; D002794:Choline; D000109:Acetylcholine