HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 89/6/2917    most recent 00996.2002v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (18) Citing Articles via Google Scholar Google Scholar Articles by Freir, D. B. Articles by Herron, C. E. Search for Related Content PubMed PubMed Citation Articles by Freir, D. B. Articles by Herron, C. E.

Nicotine Enhances the Depressive Actions of A_1–40 on Long-Term Potentiation in the Rat Hippocampal CA1 Region In Vivo

Department of Human Anatomy and Physiology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 2, Ireland

Submitted 1 November 2002; accepted in final form 6 January 2003

Hippocampal long-term potentiation (LTP) is a form of synaptic plasticity used as a cellular model of memory. Beta amyloid (A) 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 is known to bind with high affinity to the 7-nicotinic acetylcholine receptor (nAChR). Here we have investigated the effect of intracerebroventricular (icv) injection of the endogenous peptide A_1–40 on LTP in area CA1 of urethananesthetized rats. We also examined the effect of A_12–28 (icv), which binds with high affinity to the 7-nAChR and the specific 7-nAChR antagonist methyllycaconitine (MLA) on LTP. We found that A_12–28 had no effect on LTP, whereas MLA depressed significantly LTP, suggesting that activation of the 7-nAChR is a requirement for LTP. Within the in vivo environment, where other factors may compete with A_12–28 for binding to 7-nAChR, it does not appear to modulate LTP. To determine if the depressive action of A_1–40 on LTP could be modulated by nicotine, these agents were also co-applied. Injection of 1 or 10 nmol A_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_1–40 1 h prior to LTP induction caused a further significant depression of LTP compared with A_1–40 alone. These results demonstrate that nicotine enhances the deficit in LTP produced by A_1–40. This then suggests that nicotine may exacerbate the depressive actions of A on synaptic plasticity in AD.

This article has been cited by other articles:

				A. M. Minogue, A. W. Schmid, M. P. Fogarty, A. C. Moore, V. A. Campbell, C. E. Herron, and M. A. Lynch Activation of the c-Jun N-terminal Kinase Signaling Cascade Mediates the Effect of Amyloid-{beta} on Long Term Potentiation and Cell Death in Hippocampus: A ROLE FOR INTERLEUKIN-1{beta}? J. Biol. Chem., July 18, 2003; 278(30): 27971 - 27980. [Abstract] [Full Text] [PDF]

				D. B. Freir, D. A. Costello, and C. E. Herron A{beta}25-35-Induced Depression of Long-Term Potentiation in Area CA1 In Vivo and In Vitro Is Attenuated by Verapamil J Neurophysiol, June 1, 2003; 89(6): 3061 - 3069. [Abstract] [Full Text] [PDF]