title: Nicotine enhances the depressive actions of A beta 1-40 on long-term potentiation in the rat hippocampal CA1 region in vivo.
abstract: Hippocampal long-term potentiation (LTP) is a form of synaptic plasticity used as a cellular model of memory. Beta amyloid (A beta) is involved in Alzheimer's disease (AD), a neurode-generative disorder leading to cognitive deficits. Nicotine is also claimed to act as a cognitive enhancer. A beta is known to bind with high affinity to the alpha 7-nicotinic acetylcholine receptor (nAChR). Here we have investigated the effect of intracerebroventricular (i.c.v.) injection of the endogenous peptide A beta 1-40 on LTP in area CA1 of urethananesthetized rats. We also examined the effect of A beta 12-28 (i.c.v.), which binds with high affinity to the alpha 7-nAChR and the specific alpha 7-nAChR antagonist methyllycaconitine (MLA) on LTP. We found that A beta 12-28 had no effect on LTP, whereas MLA depressed significantly LTP, suggesting that activation of the alpha 7-nAChR is a requirement for LTP. Within the in vivo environment, where other factors may compete with A beta 12-28 for binding to alpha 7-nAChR, it does not appear to modulate LTP. To determine if the depressive action of A beta 1-40 on LTP could be modulated by nicotine, these agents were also co-applied. Injection of 1 or 10 nmol A beta 1-40 caused a significant depression of LTP, whereas nicotine alone (3 mg/kg) had no effect on LTP. Co-injection of nicotine with A beta 1-40 1 h prior to LTP induction caused a further significant depression of LTP compared with A beta 1-40 alone. These results demonstrate that nicotine enhances the deficit in LTP produced by A beta 1-40. This then suggests that nicotine may exacerbate the depressive actions of A beta on synaptic plasticity in AD.
authors.affiliation: Department of Human Anatomy and Physiology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 2, Ireland.
authors.forename: D B
authors.initials: DB
authors.lastname: Freir
authors.forename: C E
authors.initials: CE
authors.lastname: Herron
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000544:Alzheimer Disease / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology* / Q000503:physiopathology; D007276:Injections, Intraventricular; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects; D009538:Nicotine / Q000009:adverse effects* / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000009:adverse effects* / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D010446:Peptide Fragments; D011978:Receptors, Nicotinic; C078592:amyloid beta-protein (1-40); C092395:amyloid beta-protein (12-28); C054634:methyllycaconitine; D009538:Nicotine; D000157:Aconitine