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 alpha 7 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 alpha 7 nAChRs may contribute to the induction of LTP by nicotine, and supporting in vivo animal studies that nicotine improves learning and memory performance.