Deletion of α5 nicotine receptor subunits abolishes nicotinic aversive motivational effects in a manner that phenocopies dopamine receptor antagonism.

The European Journal of Neuroscience
Taryn E GriederD van der Kooy

Abstract

Nicotine addiction is a worldwide epidemic that claims millions of lives each year. Genetic deletion of α5 nicotinic acetylcholine receptor (nAChR) subunits has been associated with increased nicotine intake, however, it remains unclear whether acute nicotine is less aversive or more rewarding, and whether mice lacking the α5 nAChR subunit can experience withdrawal from chronic nicotine. We used place conditioning and conditioned taste avoidance paradigms to examine the effect of α5 subunit-containing nAChR deletion (α5 -/-) on conditioned approach and avoidance behaviour in nondependent and nicotine-dependent and -withdrawn mice, and compared these motivational effects with those elicited after dopamine receptor antagonism. We show that nondependent α5 -/- mice find low, non-motivational doses of nicotine rewarding, and do not show an aversive conditioned response or taste avoidance to higher aversive doses of nicotine. Furthermore, nicotine-dependent α5 -/- mice do not show a conditioned aversive motivational response to withdrawal from chronic nicotine, although they continue to exhibit a somatic withdrawal syndrome. These effects phenocopy those observed after dopamine receptor antagonism, but are not additive, suggesting t...Continue Reading

References

Sep 1, 1979·The Journal of Comparative Neurology·M Herkenham, W J Nauta
Jul 8, 1982·Brain Research·R F MuchaP Bucenieks
Jan 12, 2000·Brain Research·R IsolaM Hadjiconstantinou
Nov 19, 2002·Journal of Neurobiology·Nicolas Le NovèreJean-Pierre Changeux
Apr 16, 2003·Molecular Pharmacology·Ramiro SalasMariella De Biasi
Jan 20, 2004·Nature Neuroscience·Steven R LavioletteDerek van der Kooy
Feb 6, 2004·Psychological Review·Timothy B BakerMichael C Fiore
Jan 11, 2008·The Journal of Pharmacology and Experimental Therapeutics·K J JacksonM I Damaj
Jan 30, 2008·Molecular Psychiatry·W BerrettiniV Mooser
Jun 4, 2008·The American Journal of Psychiatry·Laura Jean BierutAlison M Goate
Mar 13, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ramiro SalasMariella De Biasi
Dec 25, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Taryn E GriederDerek van der Kooy
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Taryn E GriederDerek van der Kooy
Mar 8, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Richard ExleyStephanie J Cragg
Nov 15, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yun-Wei A HsuEric E Turner
Jun 6, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hector Vargas-PerezDerek van der Kooy

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Citations

Jul 15, 2018·Nature Communications·Shannon L WolfmanDaniel S McGehee
Nov 30, 2019·Proceedings of the National Academy of Sciences of the United States of America·Taryn E GriederDerek van der Kooy

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