Nicotine accelerates reversal of long-term potentiation and enhances long-term depression in the rat hippocampal CA1 region.
In the hippocampal CA1 region, low-frequency stimulation (LFS; 200 pulses at 1 Hz) causes reversal of long-term potentiation (depotentiation, DP) and long-term depression (LTD), both of which are thought to be the cellular substrate of learning and memory. Because nicotine enhances learning and memory, we examined if nicotine modulates DP and LTD in the hippocampal CA1 region. Bath application of nicotine during LFS accelerated DP, that is, potentiated synaptic responses in hippocampal CA1 neurons returned to pre-tetanic control levels more rapidly in the presence of nicotine. Because a similar acceleration of DP was observed using the alpha7 nicotinic acetylcholine receptor (nAChR)-selective antagonist methyllcaconitine (MLA), the nicotine effect appeared to be at least partly mediated by nicotine-induced desensitization of alpha7 nAChRs. Delivery of LFS in the presence of nicotine or MLA also depressed synaptic responses in a naive pathway and facilitated LTD, that is, the magnitude of LTD was larger when the drug was present during LFS. Thus, these results demonstrate that nicotine facilitates DP and LTD, which may represent, at least in part, the cellular mechanism underlying nicotine-induced cognitive enhancement.
Department of Neurobiology and Behavior, University of California, Irvine 92697-4550, USA.
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D000157:Aconitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology*; D007306:Insecticides / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007306:Insecticides; D018722:Nicotinic Agonists; C054634:methyllycaconitine; D009538:Nicotine; D000157:Aconitine