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The regulation of hippocampal nicotinic acetylcholine receptors (nAChRs) after a protracted treatment with selective or nonselective nAChR agonists

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Abstract

In rats, 1 mg/kg twice daily for 10 d of nicotine, a nonselective agonist of nicotinic acetylcholine receptors (nAChRs), fails to change α4 and β2 nAChR subunit mRNA but significantly decreased α7 nAChR subunit mRNA and protein expression, which is associated with a 35–40% decrease in the number of 125I-α-Bgtx binding sites in hippocampus. In addition, this schedule of nicotine treatment produced a 40% increase in the number of high- (K D 1 nM), but decreased by 25% the number of low-affinity (K D 30 nM) binding sites for 3H-epibatidine in hippocampus. In contrast, repeated treatment with lobeline (2.7 mg/kg twice daily for 10 d), which selectively binds to high-affinity binding nAChRs, fails to change the expression of high- or low-affinity nAChRs. These data suggest that a simultaneous upregulation of high-affinity nAChRs and downregulation of low-affinity nAChRs is elicited by ligands that can bind to both low- and high-affinity nAChRs, but not by selective agonists of high-affinity nAChRs. One might infer that in hippocampus, high- and low-affinity nAChRs may be located in the same cells. When these two receptor types are stimulated simultaneously by nonselective ligands for high- and low-affinity nAChRs, they interact, bringing about an increase in binding site density of the high-affinity nAChRs.

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Abbreviations

nAChR:

nicotinic acetylcholine receptor

α-Bgtx:

α-bungarotoxin

MLA:

methyllycaconitine

RT:

reverse transcriptase

PCR:

polymerase chain reaction

SDS:

sodium dodecyl sulfate

PAGE:

polyacrylamide gel electrophoresis.

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Authors and Affiliations

  1. The Psychiatric Institute Department of Psychiatry, University of Illinois College of Medicine, 60612, Chicago, IL

    James Auta, Patrizia Longone, Alessandro Guidotti & Erminio Costa

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  1. James Auta
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  2. Patrizia Longone
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  3. Alessandro Guidotti
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  4. Erminio Costa
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Auta, J., Longone, P., Guidotti, A. et al. The regulation of hippocampal nicotinic acetylcholine receptors (nAChRs) after a protracted treatment with selective or nonselective nAChR agonists. J Mol Neurosci 13, 31–45 (1999). https://doi.org/10.1385/JMN:13:1-2:31

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  • DOI: https://doi.org/10.1385/JMN:13:1-2:31

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