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The Journal of Neuroscience, December 1, 2000, 20(23):8802-8811
Long-Term Nicotine Adaptation in Caenorhabditis
elegans Involves PKC-Dependent Changes in Nicotinic Receptor
Abundance
Laura E.
Waggoner1,
Kari A.
Dickinson1,
Daniel
S.
Poole1,
Yo
Tabuse2,
Johji
Miwa2, and
William R.
Schafer1
1 Department of Biology, University of California, San
Diego, La Jolla, California 92093-0349, and 2 Fundamental
Research Laboratories, NEC Corporation, Tsukuba 305, Japan
Chronic exposure to nicotine leads to long-term changes in both the
abundance and activity of nicotinic acetylcholine receptors, processes thought to contribute to nicotine addiction. We have found
that in Caenorhabditis elegans, prolonged nicotine
treatment results in a long-lasting decrease in the abundance of
nicotinic receptors that control egg-laying. In naive animals, acute
exposure to cholinergic agonists led to the efficient stimulation of
egg-laying, a response mediated by a nicotinic receptor functionally
expressed in the vulval muscle cells. Overnight exposure to nicotine
led to a specific and long-lasting change in egg-laying behavior, which
rendered the nicotine-adapted animals insensitive to simulation of
egg-laying by the nicotinic agonist and was accompanied by a
promoter-independent reduction in receptor protein levels. Mutants defective in the gene tpa-1, which encodes a homolog of
protein kinase C (PKC), failed to undergo adaptation to nicotine; after chronic nicotine exposure they remained sensitive to cholinergic agonists and retained high levels of receptor protein in the vulval muscles. These results suggest that PKC-dependent signaling pathways may promote nicotine adaptation via regulation of nicotinic receptor synthesis or degradation.
Key words:
nicotinic; acetylcholine; Caenorhabditis
elegans; protein kinase C; adaptation; levamisole
Copyright © 2000 Society for Neuroscience 0270-6474/00/20238802-10$05.00/0
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