Epibatidine induces long-term potentiation (LTP) via activation of alpha4beta2 nicotinic acetylcholine receptors (nAChRs) in vivo in the intact mouse dentate gyrus: both alpha7 and alpha4beta2 nAChRs essential to nicotinic LTP.
Activation of nicotinic acetylcholine receptors (nAChRs) induces nocotinic long-term potentiation (LTPn) in vivo in the mouse dentate gyrus. We have found that alpha4beta2 nAChRs activated by epibatidine induce LTPn, the full size of which requires the involvement of alpha4beta2 and alpha7 nAChRs, in the intact mouse dentate gyrus using extracellular recording techniques. Intraperitoneal application of epibatidine, a potent alpha4beta2 nAChR agonist, at 0.3 - 3.0 mug/kg induced a long-lasting increase similar to LTPn induced by choline, a selective alpha7 nAChR agonist, and at 10 mug/kg caused a transient increase followed by a depression. The LTPn induced by epibatidine at 3.0 mug/kg or choline at 30 mg/kg was significantly suppressed by pre-treatment but not post-treatment with mecamylamine (0.5 mg/kg, i.p.), a non-selective neuronal nicotinic antagonist. Post-application of nicotine at 3.0 mg/kg enhanced epibatidine-induced LTPn to the same level of nicotine-induced LTPn, but post-application of epibatidine had no effect on nicotine-induced LTPn. Epibatidine-induced LTPn was additionally increased by post-application of choline, and vice versa, reaching the same level of nicotine-induced LTPn. The present study revealed that epibatidine induced the LTPn via alpha4beta2 nAChRs and that both alpha7 and alpha4beta2 nAChRs were essential for full-sized LTPn, suggesting that both nAChRs play an important role in synaptic plasticity.
Division of Molecular Pharmacology and Pharmacogenomics, Department of Genome Sciences, Kobe University Graduate School of Medicine, Japan. shogo@med.kobe-u.ac.jp
Shogo
S
Matsuyama
Akira
A
Matsumoto
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002794:Choline / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects*; D004357:Drug Synergism; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D019086:Bridged Bicyclo Compounds, Heterocyclic; C579166:Chrna7 protein, mouse; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; D008464:Mecamylamine; D009538:Nicotine; C082748:epibatidine; D002794:Choline