Academic Journal
Body Temperature and Discriminative Stimulus Effects of Nicotine and Menthol Aerosols in Male Rats: Role of α4β2 Nicotinic Acetylcholine Receptors.
| Τίτλος: | Body Temperature and Discriminative Stimulus Effects of Nicotine and Menthol Aerosols in Male Rats: Role of α4β2 Nicotinic Acetylcholine Receptors. |
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| Συγγραφείς: | Eom TI; Department of Physiology, College of Korean Medicine, Daegu Haany University, 1 Haanydaero, Gyeongsan-si, Gyeongsangbuk-do38610, Republic of Korea., Jang PK; Department of Physiology, College of Korean Medicine, Daegu Haany University, 1 Haanydaero, Gyeongsan-si, Gyeongsangbuk-do38610, Republic of Korea., Nam J; College of Pharmacy, Keimyung University, 1095 Dalgubeol-Daero, Dalseo-gu, Daegu42601, Republic of Korea., Kim S; College of Pharmacy, Keimyung University, 1095 Dalgubeol-Daero, Dalseo-gu, Daegu42601, Republic of Korea., Lee BH; Department of Acupuncture, Moxibustion and Acupoint, College of Korean Medicine, Daegu Haany University, 1 Haanydaero, Gyeongsan-si, Gyeongsangbuk-do38610, Republic of Korea., Chang S; Department of Acupuncture, Moxibustion and Acupoint, College of Korean Medicine, Daegu Haany University, 1 Haanydaero, Gyeongsan-si, Gyeongsangbuk-do38610, Republic of Korea., Cha HJ; College of Veterinary Medicine, Gyeongsang National University, Jinju52828, Republic of Korea., Yun J; College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-Ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk28160, Republic of Korea., Yang CH; Department of Physiology, College of Korean Medicine, Daegu Haany University, 1 Haanydaero, Gyeongsan-si, Gyeongsangbuk-do38610, Republic of Korea., Lee S; College of Pharmacy, Keimyung University, 1095 Dalgubeol-Daero, Dalseo-gu, Daegu42601, Republic of Korea., Yoon SS; Department of Physiology, College of Korean Medicine, Daegu Haany University, 1 Haanydaero, Gyeongsan-si, Gyeongsangbuk-do38610, Republic of Korea. |
| Πηγή: | ACS chemical neuroscience [ACS Chem Neurosci] 2026 Sep 02; Vol. 17 (17), pp. 3203-3216. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101525337 Publication Model: Print Cited Medium: Internet ISSN: 1948-7193 (Electronic) Linking ISSN: 19487193 NLM ISO Abbreviation: ACS Chem Neurosci Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, D.C. : American Chemical Society |
| Ιατρικοί όροι (MeSH): | Menthol*/pharmacology , Menthol*/administration & dosage , Nicotine*/pharmacology , Nicotine*/blood , Nicotine*/administration & dosage , Nicotine*/pharmacokinetics , Receptors, Nicotinic*/metabolism , Body Temperature*/drug effects , Nicotinic Agonists*/pharmacology , Discrimination, Psychological*/drug effects, Dihydro-beta-Erythroidine/pharmacology ; Cotinine/analogs & derivatives ; Cotinine/blood ; Animals ; Male ; Aerosols ; Rats, Sprague-Dawley ; Rats ; Dose-Response Relationship, Drug |
| Περίληψη: | Menthol, a prevalent additive in tobacco and electronic cigarette products, has been reported to interact with nicotine at both neuropharmacological and behavioral levels. Although menthol alone is not reinforcing, converging evidence suggests that it may modulate the pharmacological and behavioral effects of nicotine through nicotinic acetylcholine receptor (nAChR) mechanisms. Using an inhalation-based rodent model that mimics human exposure to electronic nicotine delivery systems, we examined how menthol aerosol influences nicotine-induced hypothermia, discriminative stimulus effects, and the potential involvement of α4β2* nAChRs in male rats. Plasma nicotine, cotinine, and trans-3'-hydroxycotinine (3'-OH-cotinine) concentrations were also measured to assess pharmacokinetic interactions. Menthol aerosol prolonged and potentiated nicotine-induced hypothermia, and this effect was attenuated by the α4β2* receptor antagonist dihydro-β-erythroidine (DHβE). In drug discrimination (DD) assays, coinhalation of menthol enhanced nicotine-appropriate responding, suggesting facilitation of nicotine's interoceptive stimulus properties. These effects were also attenuated by DHβE, consistent with involvement of α4β2* nAChR-mediated mechanisms. In addition, the behavioral effects were accompanied by alterations in nicotine pharmacokinetics, including increased levels of nicotine metabolites. Collectively, these findings suggest that menthol modulates nicotine's pharmacological and behavioral effects, potentially through α4β2* nAChR-dependent mechanisms. By prolonging nicotine's physiological and interoceptive effects, menthol may increase the salience of nicotine-related cues during inhalation exposure. These interactions could contribute to enhanced abuse liability associated with menthol-containing nicotine products, although further studies are required to establish causal mechanisms. This study provides mechanistic insight into menthol-nicotine interactions and highlights considerations relevant to mentholated e-cigarette products. (© 2026 American Chemical Society.) |
| Grant Information: | 25212MFDS003 Ministry of Food and Drug Safety; 2019R1I1A1A01052581 National Research Foundation of Korea; 2022R1A2C1005828 National Research Foundation of Korea |
| Contributed Indexing: | Keywords: body temperature; discriminative-stimulus effects; electronic nicotine delivery systems; menthol; nicotine; α4β2* nicotinic acetylcholine receptor |
| Substance Nomenclature: | 1490-04-6 (Menthol) 6M3C89ZY6R (Nicotine) 0 (Receptors, Nicotinic) 0 (nicotinic receptor alpha4beta2) 0 (Aerosols) 0 (Nicotinic Agonists) 23255-54-1 (Dihydro-beta-Erythroidine) K5161X06LL (Cotinine) 27323-64-4 (hydroxycotinine) |
| Entry Date(s): | Date Created: 20260903 Date Completed: 20260903 Latest Revision: 20260903 |
| Update Code: | 20260904 |
| DOI: | 10.1021/acschemneuro.6c00295 |
| PMID: | 42690720 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1948-7193 |
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| DOI: | 10.1021/acschemneuro.6c00295 |