+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Hippocampal alpha 7 and alpha 4 beta 2 nicotinic receptors and working memory



Hippocampal alpha 7 and alpha 4 beta 2 nicotinic receptors and working memory



Neuroscience 109(4): 757-765



Nicotine and other nicotinic receptor agonists have been found in a variety of studies to improve memory, while nicotinic receptor blockade can impair memory. The critical neural mechanisms for nicotinic involvement with memory are still under investigation. Initial evidence supports the involvement of the ventral hippocampus. Lesions in this area block nicotine-induced memory improvement and mecamylamine-induced impairment. Local ventral hippocampal application of the nicotinic channel blocker mecamylamine impairs memory in the 8-arm radial maze. Both alpha 4 beta 2 and alpha 7 nicotinic receptors seem to be involved. Ventral hippocampal infusions of high doses of the alpha 4 beta 2 nicotinic antagonist dihydro-beta-erythrodine (DH beta E) and the alpha 7 nicotinic antagonist methyllycaconitine (MLA) impair memory performance on the 8-arm radial maze. However, high doses of these drugs may limit specificity and they cause preconvulsant effects, which in themselves may affect memory. The current study used the more challenging 16-arm radial maze to determine the effects of lower doses of these drugs on memory and to differentiate effects on working and reference memory. Adult female Sprague-Dawley rats were trained on a working and reference memory task in the 16-arm radial maze and then were implanted with bilateral chronic guide cannulae directed to the ventral hippocampus. After recovery from surgery, the rats received acute intrahippocampal infusions of dose combinations of DH beta E and MLA. In the first study, DH beta E (0 and 6.75 microg/side) and MLA (0, 6.75, 13.5 and 27 microg/side) were administered in a counter-balanced order. In the second study, lower doses of DH beta E (0, 1.6375, 3.275 and 6.75 microg/side) were administered alone or with MLA (0 and 6.75 microg/side) in a counter-balanced order. In the first study, DH beta E caused a significant increase in both working and reference memory errors. MLA at a dose of 27 microg/side caused a significant increase in working memory errors, but this dose had no significant effect on reference memory errors. Interestingly, no additive effects were seen with combined administration of DH beta E and MLA in this study, and at the doses used, no effects were seen on response latency. In the second study, lower doses of DH beta E did not cause a significant deficit in working memory performance. Co-administration of MLA with these subthreshold doses did precipitate a memory impairment. The current results confirm the specificity of the memory deficits caused by these drugs. These results support the involvement of alpha 4 beta 2 and alpha 7 nicotinic receptors in the ventral hippocampus as being critical for memory function.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 046257150

Download citation: RISBibTeXText

PMID: 11927157


Related references

Pharmacological characterization of recombinant human neuronal nicotinic acetylcholine receptors h alpha 2 beta 2, h alpha 2 beta 4, h alpha 3 beta 2, h alpha 3 beta 4, h alpha 4 beta 2, h alpha 4 beta 4 and h alpha 7 expressed in Xenopus oocytes. Journal of Pharmacology and Experimental Therapeutics 280(1): 346-356, 1997

Comparative levels of nicotinic alpha-4-beta-2/ cytisine and alpha-7 alpha-bungarotoxin receptors in aged memory-impaired and memory-unimpaired Long Evans rats. Society for Neuroscience Abstracts 21(1-3): 1334, 1995

Ventral hippocampal alpha 7 and alpha 4 beta 2 nicotinic receptor blockade and clozapine effects on memory in female rats. Psychopharmacology 188(4): 597-604, 2006

Structural differences determine the relative selectivity of nicotinic compounds for native alpha 4 beta 2*-, alpha 6 beta 2*-, alpha 3 beta 4*- and alpha 7-nicotine acetylcholine receptors. Neuropharmacology 58(7): 1054-1066, 2010

The A beta(1-42)M35C mutated amyloid peptide A beta(1-42)and the 25-35 fragment fail to mimic the subtype-specificity of actions on recombinant human nicotinic acetylcholine receptors (alpha 7, alpha 4 beta 2, alpha 3 beta 4). Neuroscience Letters 427(1): 28-33, 2007

Subtype-specific actions of beta-amyloid peptides on recombinant human neuronal nicotinic acetylcholine receptors (alpha 7, alpha 4 beta 2, alpha 3 beta 4) expressed in Xenopus laevis oocytes. British Journal of Pharmacology 146(7): 964-971, 2005

Alpha 4 beta 2 neuronal nicotinic acetylcholine receptors in the central nervous system are inhibited by isoflurane and propofol, but alpha 7-type nicotinic acetylcholine receptors are unaffected. Anesthesiology 86(4): 859-865, 1997

Comparative structure of human neuronal alpha 2-alpha 7 and beta 2-beta 4 nicotinic acetylcholine receptor subunits and functional expression of the alpha 2, alpha 3, alpha 4, alpha 7, beta 2, and beta 4 subunits. Journal of Molecular Neuroscience 7(3): 217-228, 1996

Regions of beta 2 and beta 4 responsible for differences between the steady state dose-response relationships of the alpha 3 beta 2 and alpha 3 beta 4 neuronal nicotinic receptors. Journal of General Physiology 105(6): 745-764, 1995

Ca+2 modulation of alpha-4-beta-2 and alpha-4-alpha-5-beta-2 combinations of neuronal nicotinic receptors. Society for Neuroscience Abstracts 22(1-3): 1526, 1996

Beta -Amyloid peptide blocks the response of alpha 7-containing nicotinic receptors on hippocampal neurons. Proceedings of the National Academy of Sciences of the United States of America 98(8): 4734-4739, 2001

Role of alpha-5 subunit in determining relationship of peak to late-phase current in human alpha-3-beta-2-alpha-5 neuronal nicotinic acetylcholine receptors. Society for Neuroscience Abstracts 23(1-2): 390, 1997

An acute effect of neuregulin 1 beta to suppress alpha 7-containing nicotinic acetylcholine receptors in hippocampal interneurons. Journal of Neuroscience 26(44): 11295-11303, 2006

The loop between beta-strands beta 2 and beta 3 and its interaction with the N-terminal alpha-helix is essential for biogenesis of alpha 7 nicotinic receptors. Journal of Neurochemistry 112(1): 103-111, 2010

Thymocytes and cultured thymic epithelial cells express transcripts encoding alpha-3, alpha-5 and beta-4 subunits of neuronal nicotinic acetylcholine receptors: preferential transcription of the alpha-3 and beta-4 genes by immature CD4 + 8 + thymocytes. Journal of Neuroimmunology 79(2): 176-184, 1997