2016
DOI: 10.1097/fbp.0000000000000233
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Differential antagonism and tolerance/cross-tolerance among nicotinic acetylcholine receptor agonists

Abstract: The tobacco dependence pharmacotherapies varenicline and cytisine act as partial α4β2 nAChR agonists. However, the extent to which α4β2 nAChRs mediate their in vivo effects remains unclear. Nicotine, varenicline, cytisine, and epibatidine were studied in male C57BL/6J mice for their effects on rates of fixed ratio responding and rectal temperature, alone and in combination with the nonselective nAChR antagonist mecamylamine and the α4β2 nAChR antagonist DHβE. The effects of nicotine, varenicline, cytisine, epi… Show more

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Cited by 10 publications
(26 citation statements)
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“…Mecamylamine failed to antagonize the rate-decreasing effects of nicotine and varenicline, which contradicts previous studies demonstrating that the rate-decreasing effects of nicotine and varenicline were antagonized by mecamylamine (de Moura and McMahon 2016). However, this current study and the de Moura and McMahon (2016) study differed in the amount of nicotine and varenicline exposure the mice received.…”
Section: Discussioncontrasting
confidence: 90%
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“…Mecamylamine failed to antagonize the rate-decreasing effects of nicotine and varenicline, which contradicts previous studies demonstrating that the rate-decreasing effects of nicotine and varenicline were antagonized by mecamylamine (de Moura and McMahon 2016). However, this current study and the de Moura and McMahon (2016) study differed in the amount of nicotine and varenicline exposure the mice received.…”
Section: Discussioncontrasting
confidence: 90%
“…Mecamylamine failed to antagonize the rate-decreasing effects of nicotine and varenicline, which contradicts previous studies demonstrating that the rate-decreasing effects of nicotine and varenicline were antagonized by mecamylamine (de Moura and McMahon 2016). However, this current study and the de Moura and McMahon (2016) study differed in the amount of nicotine and varenicline exposure the mice received. Repeated exposure to nicotine and varenicline in the current study, which was greater than in the de Moura and McMahon (2016) experiment prior to chronic nicotine treatment, may have diminished the capacity of mecamylamine to antagonize the rate-decreasing effects of nicotine and varenicline.…”
Section: Discussioncontrasting
confidence: 90%
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“…However, extremely high level of nicotine results in hypotension and reduced heart rate intermediated by peripheral ganglionic blockade or central nervous system (N. L. Benowitz, 1988). In addition, the tolerance of nicotine is developed after repeated doses, which may cause adverse effects of nausea, vomiting and pallor and so on (Moura & McMahon, 2016).…”
Section: Historical Backgroundmentioning
confidence: 99%