Acute and chronic nicotine exposure reverse age-related declines in the induction of long-term potentiation in the rat hippocampus

• Published in: Brain research 2001-03, Vol.894 (2), p.347-353
• Main Authors: Fujii, Satoshi, Sumikawa, Katumi
• Format: Article
• Language: English
• Subjects: Aconitine - analogs & derivatives; Aconitine - pharmacology; Aged rat; Aging - physiology; alpha7 Nicotinic Acetylcholine Receptor; Animals; Biological and medical sciences; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Hippocampus; Hippocampus - drug effects; Hippocampus - physiology; Insecticides - pharmacology; Long-term potentiation; Long-Term Potentiation - drug effects; Long-Term Potentiation - physiology; Medical sciences; Membrane Potentials - drug effects; Membrane Potentials - physiology; Methyllycaconitine; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Nicotine; Nicotine - pharmacology; Nicotinic acetylcholine receptor; Nicotinic Agonists - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic - physiology; Synaptic plasticity; Tobacco, tobacco smoking; Toxicology
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(01)02057-1

Long-term potentiation (LTP) is widely considered to be the cellular substrate of learning and memory. The induction of LTP becomes more difficult with age in parallel with declining learning and memory ability. Because nicotine improves learning and memory in aged rats, we examined the effects of acute and chronic nicotine exposure on age-related declines in LTP induction. We found that acute nicotine exposure lowered the threshold for LTP induction in the aging hippocampus. The effect of nicotine was mimicked by the α7 nicotinic acetylcholine receptor (nAChR) antagonist methyllycaconitine and blocked by the non-α7 nAChR antagonist dihydro-β-erythroidine, suggesting that both nicotine-mediated desensitization of α7 nAChRs and activation of non-α7 nAChRs contribute to the nicotine effect. The non-α7 nAChR agonist A85380 that facilitates the induction of LTP in the young hippocampus had no effect, however, suggesting that at least one pathway involving non-α7 nAChRs was altered by aging. Chronic nicotine treatment of aged rats also lowered the threshold for LTP induction and acute nicotine exposure lowered the threshold further in the chronic-nicotine-treated aged hippocampus. These results not only suggest that the mechanisms mediated by acute and chronic nicotine exposure are different, but also demonstrate that age-associated declines in LTP induction can be reversed with nicotine treatment.