title: Differential discriminative-stimulus effects of cigarette smoke condensate and nicotine in nicotine-discriminating rats.
abstract: Although it is widely accepted that nicotine plays a key role in tobacco dependence, nicotine alone cannot account for all of the pharmacological effects associated with cigarette smoke found in preclinical models. Thus, the present study aimed to determine the differential effects of the interoceptive cues of nicotine alone versus those of cigarette smoke condensate (CSC) in nicotine-trained rats. First, the rats were trained to discriminate nicotine (0.4mg/kg, subcutaneous [s.c.]) from saline in a two-lever drug discrimination paradigm. Then, to clarify the different neuropharmacological mechanisms underlying the discriminative-stimulus effects in the nicotine and CSC in nicotine-trained rats, either the α4β2 nicotinic acetylcholine receptor (nAChR) antagonist dihydro-β-erythroidine (DHβE; 0.3-1.0mg/kg, s.c.) or the α7 nAChR antagonist methyllycaconitine citrate (MLA; 5-10mg/kg, intraperitoneal [i.p.]) was administered prior to the injection of either nicotine or CSC. Separate set of experiments was performed to compare the duration of action of the discriminative-stimulus effects of CSC and nicotine. CSC exhibited a dose-dependent nicotine generalization, and interestingly, 1.0mg/kg of DHβE antagonized the discriminative effects of nicotine (0.4mg/kg) but not CSC (0.4mg/kg nicotine content). However, pretreatment with MLA had no effect. In the time-course study, CSC had a relatively longer half-life in terms of the discriminative-stimulus effects compared with nicotine alone. Taken together, the present findings indicate that CSC has a distinct influence on interoceptive effects relative to nicotine alone and that these differential effects might be mediated, at least in part, by the α4β2, but not the α7, nAChR.
authors.affiliation: Research Center for Safety Pharmacology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea; Department of Toxicology Evaluation, Konyang University, Daejeon 35365, Republic of Korea.
authors.forename: Jun-Yeob
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Research Center for Safety Pharmacology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea; Department of Toxicology Evaluation, Konyang University, Daejeon 35365, Republic of Korea.
authors.forename: Mee Jung
authors.initials: MJ
authors.lastname: Choi
authors.affiliation: Department of Biological Sciences, Pusan National University, Pusan 46241, Republic of Korea.
authors.forename: Eun Sang
authors.initials: ES
authors.lastname: Choe
authors.affiliation: Research Center for Safety Pharmacology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea.
authors.forename: Young-Ju
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Research Center for Safety Pharmacology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea. Electronic address: jwseo@kitox.re.kr.
authors.forename: Joung-Wook
authors.initials: JW
authors.lastname: Seo
authors.affiliation: Research Center for Safety Pharmacology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea. Electronic address: ssyoon@kitox.re.kr.
authors.forename: Seong Shoon
authors.initials: SS
authors.lastname: Yoon
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects*; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking / Q000523:psychology; D013997:Time Factors
chemical_list: D018722:Nicotinic Agonists; C054634:methyllycaconitine; D004079:Dihydro-beta-Erythroidine; D009538:Nicotine; D000157:Aconitine
keywords: Cigarette smoke condensate; Drug discrimination; Nicotine; Nicotinic acetylcholine receptors; Rats