{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:59:47Z","timestamp":1787507987349,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,2,24]],"date-time":"2020-02-24T00:00:00Z","timestamp":1582502400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R01\u2010DA25267"],"award-info":[{"award-number":["R01\u2010DA25267"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["UG3\u2010DA48353"],"award-info":[{"award-number":["UG3\u2010DA48353"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>There is a long\u2010standing interest in developing nicotinic acetylcholine receptor (nAChR) antagonists for concomitant use with nAChR agonists (e.g., nicotine replacement) as complementary smoking cessation aids. Previous studies demonstrate that daily nicotine treatment confers tolerance to some effects of nicotine, as well as cross\u2010tolerance to other nAChR agonists. The current study assessed the extent to which antagonism of nicotine varies as a function of daily nicotine treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Schedule\u2010controlled responding and hypothermia were selected for study because they have been previously used to examine the pharmacology of nicotine, and both are sensitive to the development nicotine tolerance. The rate\u2010decreasing and hypothermic effects of nicotine, as well as antagonism of those effects, were examined in C57BL\/6J mice before, during treatment with, and after discontinuation of three daily injections of 1.78\u00a0mg\/kg nicotine. The nonselective nAChR antagonist mecamylamine and the \u03b22 nAChR antagonist dihydro\u2010\u03b2\u2010erythroidine (DH\u03b2E) were studied in combination with nicotine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The ED\n                      <jats:sub>50<\/jats:sub>\n                      values of nicotine to produce rate\u2010decreasing and hypothermic effects were, respectively, 0.44 and 0.82\u00a0mg\/kg prior, 1.6 and 3.2\u00a0mg\/kg during, and 0.74 and 1.1\u00a0mg\/kg after discontinuation of daily nicotine treatment. Prior to daily nicotine treatment, mecamylamine decreased response rate and rectal temperature. However, during daily nicotine, mecamylamine (up to 5.6\u00a0mg\/kg) only decreased rectal temperature. DH\u03b2E (up to 5.6\u00a0mg\/kg) when studied prior to daily nicotine decreased rectal temperature, but that decrease was abolished during chronic nicotine treatment. Mecamylamine and DH\u03b2E antagonized the rate\u2010decreasing and hypothermic effects of nicotine before and after daily nicotine; however, during daily nicotine, mecamylamine and DH\u03b2E antagonized only the hypothermic effects of nicotine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The differential antagonism of rate\u2010decreasing and hypothermic effects implicates differential involvement of nAChR subtypes. The decreased capacity of mecamylamine and DH\u03b2E to antagonize nicotine during chronic nicotine treatment may indicate that their effectiveness as smoking cessations might vary as a function of nicotine tolerance and dependence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.1581","type":"journal-article","created":{"date-parts":[[2020,2,24]],"date-time":"2020-02-24T15:58:06Z","timestamp":1582559886000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unexpected loss of sensitivity to the nicotinic acetylcholine receptor antagonist activity of mecamylamine and dihydro\u2010\u03b2\u2010erythroidine in nicotine\u2010tolerant mice"],"prefix":"10.1002","volume":"10","author":[{"given":"Fernando B.","family":"de Moura","sequence":"first","affiliation":[{"name":"Department of Pharmacology The University of Texas Health Science Center at San Antonio San Antonio TX USA"},{"name":"Behavioral Biology 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