{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T13:03:12Z","timestamp":1772456592753,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T00:00:00Z","timestamp":1725926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31871865"],"award-info":[{"award-number":["31871865"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["BJ2023030"],"award-info":[{"award-number":["BJ2023030"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2024KF0278"],"award-info":[{"award-number":["2024KF0278"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Top Talent Support Program for young and middle-aged people of Wuxi Health Committee","award":["31871865"],"award-info":[{"award-number":["31871865"]}]},{"name":"Top Talent Support Program for young and middle-aged people of Wuxi Health Committee","award":["BJ2023030"],"award-info":[{"award-number":["BJ2023030"]}]},{"name":"Top Talent Support Program for young and middle-aged people of Wuxi Health Committee","award":["2024KF0278"],"award-info":[{"award-number":["2024KF0278"]}]},{"name":"Qilu Clinical Research Foundation of Nanjing Medical University","award":["31871865"],"award-info":[{"award-number":["31871865"]}]},{"name":"Qilu Clinical Research Foundation of Nanjing Medical University","award":["BJ2023030"],"award-info":[{"award-number":["BJ2023030"]}]},{"name":"Qilu Clinical Research Foundation of Nanjing Medical University","award":["2024KF0278"],"award-info":[{"award-number":["2024KF0278"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Nicotine dependence is an important cause of excessive exposure to tobacco combustion compounds in most smokers. Nicotine replacement therapy is the main method to treat nicotine dependence, but it still has its shortcomings, such as the inability to mitigate withdrawal effects and limited applicability. It has been hypothesized that a combination of low-dose nicotine and caffeine could achieve the same psychological stimulation effect as a high dose of nicotine without causing nicotine withdrawal effects. To establish a model of nicotine dependence, male C57BL\/6J mice were subcutaneously injected four times a day with nicotine (2 mg\/kg) for 15 days and fed with water containing nicotine at the same time. They were randomly divided into four groups. After 24 h of withdrawal, different groups were injected with saline, nicotine (0.25 mg\/kg or 0.1 mg\/kg), or nicotine (0.1 mg\/kg) and caffeine (20 mg\/kg). Behavioral and physiological changes were evaluated by an assessment of physical signs, open field tests, elevated plus maze experiments, forced swimming tests, hot plate tests, and new-object-recognition tests. The changes in dopamine release in the prefrontal cortex (PFC) and ventral tegmental area (VTA) in the midbrain were analyzed using ELISA. The results showed that a combination of caffeine and nicotine could effectively relieve nicotine withdrawal syndrome, increase movement ability and pain thresholds, reduce anxiety and depression, enhance memory and cognitive ability, and increase the level of dopamine release in the PFC and VTA. Thus, caffeine combined with nicotine has potential as a stable and effective treatment option to help humans with smoking cessation.<\/jats:p>","DOI":"10.3390\/nu16183048","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T03:16:51Z","timestamp":1725938211000},"page":"3048","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Effect of a Caffeine and Nicotine Combination on Nicotine Withdrawal Syndrome in Mice"],"prefix":"10.3390","volume":"16","author":[{"given":"Zhe","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Oncology, The Affiliated Wuxi People\u2019s Hospital of Nanjing Medical University, Wuxi People\u2019s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9778-2819","authenticated-orcid":false,"given":"Naiyan","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"Sports and Health Research Institute, Jiangnan University, Wuxi 214122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Li","sequence":"additional","affiliation":[{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingrun","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujie","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiyue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Jiangnan University Medical Center, Jiangnan University, Wuxi 214126, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ximiao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Jiangnan University Medical Center, Jiangnan University, Wuxi 214126, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haotian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Sports and Health Research Institute, Jiangnan University, Wuxi 214122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7867-6807","authenticated-orcid":false,"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Sport Science, Beijing Sport University, Beijing 100084, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Jiangnan University Medical Center, Jiangnan University, Wuxi 214126, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weisun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Wuxi People\u2019s Hospital of Nanjing Medical University, Wuxi People\u2019s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sansone, L., Milani, F., Fabrizi, R., Belli, M., Cristina, M., Zaga, V., de Iure, A., Cicconi, L., Bonassi, S., and Russo, P. 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