Activation of nicotinic acetylcholine receptors induces long-term potentiation in vivo in the intact mouse dentate gyrus.
The present study was conducted to clarify the role of nicotinic ACh receptors (nAChRs) on long-term potentiation (LTP) in vivo in the intact mouse dentate gyrus using extracellular recording techniques. Intraperitoneal application of nicotine at a dose of 3.0 mg/kg but not 0.03 or 0.3 mg/kg produced a gradually developing, long-lasting increase for 120 min similar to tetanic LTP. Nicotine at a dose of 9. 0 mg/kg caused a temporary increase followed by depression. The long-lasting potentiation induced by nicotine at 3.0 mg/kg, which was named nicotinic long-term potentiation (LTPn), and tetanic LTP were significantly suppressed by pretreatment with mecamylamine (0.5 mg/kg i.p.), a nonselective nicotinic antagonist, but not affected by postapplication of mecamylamine. Interestingly, choline, a selective alpha7 nAChR agonist, at 3.0-90 mg/kg, induced the long-lasting potentiation similar to LTPn in a dose-dependent manner in vivo in the intact mouse dentate gyrus. The long-lasting potentiation induced by choline (30 mg/kg i.p.) was additionally increased by postapplication of nicotine (3.0 mg/kg i.p.) or tetanic stimulation. The present study revealed that systemic application of nicotine or choline induced the long-lasting potentiation in vivo in the intact mouse dentate gyrus, suggesting that alpha7 nAChRs may contribute to the induction of LTP by nicotine, and supporting in vivo animal studies that nicotine improves learning and memory performance.
Matsuyama
S
S
Department of Pharmacology, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. shogo@med.kobe-u.ac.jp
Matsumoto
A
A
Enomoto
T
T
Nishizaki
T
T
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002794:Choline / Q000494:pharmacology; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008464:Mecamylamine / Q000494:pharmacology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014029:Tobacco Use Disorder / Q000378:metabolism / Q000503:physiopathology; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579166:Chrna7 protein, mouse; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D008464:Mecamylamine; D009538:Nicotine; D002794:Choline; D000109:Acetylcholine