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Enhanced cocaine dependence in adulthood following adolescent nicotine exposure is significantly associated with elevated CCL5 expression
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Fan YE1, Hong-wan DING1, Li-bo ZHANG2, 3, *, Gui-bin WANG1, *, Jian-jun ZHANG1, *
Acta Pharmaceutica Sinica | 2025, 60(7) : 2211 - 2217
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Acta Pharmaceutica Sinica | 2025, 60(7): 2211-2217
• Original Articles •
Enhanced cocaine dependence in adulthood following adolescent nicotine exposure is significantly associated with elevated CCL5 expression
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Fan YE1, Hong-wan DING1, Li-bo ZHANG2, 3, *, Gui-bin WANG1, *, Jian-jun ZHANG1, *
Affiliations
  • 1Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
  • 2Beijing Key Laboratory of Drug Dependence Research, National Institute on Drug Dependence, Peking University, Beijing 100191, China
  • 3Shenzhen Hospital, Peking University, Shenzhen 518036, China
Published: 2025-07-12 doi: 10.16438/j.0513-4870.2025-0107
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This study aims to investigate the effects of nicotine exposure during puberty on cocaine addiction behaviors in adult rats and to investigate the underlying mechanisms. Male Wistar rats, aged 30 days, were divided into two groups: saline-exposed group and nicotine-exposed group. The nicotine-exposed group received subcutaneous injections (sc) of 0.3 mg·kg-1 nicotine solution three times daily for 15 consecutive days, while the saline-exposed group received an equal volume of saline. On day 60 post-birth, blood was collected from the orbital sinus to separate serum. On day 62, rats underwent jugular vein catheterization surgery and self-administration (SA) training for cocaine, which lasted for 10 consecutive days. The fixed ratio (FR) schedule was gradually increased. After training, rats displayed stable nose-poke behavior for cocaine seeking. Dose-response tests (DR) and progressive ratio tests (PR) were performed to examine whether nicotine exposure during adolescence influenced cocaine addiction in adulthood. This experiment was approved by the Animal Ethics Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences (approval number: 00004401). In the DR test, nicotine-exposed rats showed significantly higher numbers of effective cocaine injections at doses of 0.03, 0.1, and 0.3 mg·kg-1 compared to the saline-exposed group. The nicotine-exposed group exhibited more pronounced craving for cocaine. In the PR test, at 0.75 mg·kg-1 cocaine dose, nicotine-exposed rats tended to have higher breakpoints (BP) than the saline-exposed group. Cytokine antibody array and ELISA of serum revealed that CCL5 level in the nicotine-exposed group was significantly higher than that in the saline-exposed group. Moreover, in the DR test, the number of cocaine injections obtained at 0 and 0.3 mg·kg-¹ cocaine doses correlated significantly with CCL5 levels. In conclusion, nicotine administration during puberty in rats can significantly increase their addiction to cocaine and self-administration behavior in adulthood, exhibiting distinct drug dependence characteristics. The content of CCL5 in rat serum is positively correlated with cocaine addictive behavior.

nicotine  /  cocaine  /  addiction  /  self-administration  /  C-C motif chemokine ligand 5
叶凡, 丁虹琬, 张力博, 王贵彬, 张建军. 青春期摄入尼古丁的大鼠成年期对可卡因依赖性增强与CCL5高表达显著相关. 药学学报, 2025 , 60 (7) : 2211 -2217 . DOI: 10.16438/j.0513-4870.2025-0107
Fan YE, Hong-wan DING, Li-bo ZHANG, Gui-bin WANG, Jian-jun ZHANG. Enhanced cocaine dependence in adulthood following adolescent nicotine exposure is significantly associated with elevated CCL5 expression[J]. Acta Pharmaceutica Sinica, 2025 , 60 (7) : 2211 -2217 . DOI: 10.16438/j.0513-4870.2025-0107
Year 2025 volume 60 Issue 7
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129
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Article Info
doi: 10.16438/j.0513-4870.2025-0107
  • Receive Date:2025-02-07
  • Online Date:2026-09-20
  • Published:2025-07-12
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History
  • Received:2025-02-07
  • Revised:2025-04-03
Affiliations
    1Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
    2Beijing Key Laboratory of Drug Dependence Research, National Institute on Drug Dependence, Peking University, Beijing 100191, China
    3Shenzhen Hospital, Peking University, Shenzhen 518036, China
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表12种不同金属材料的力学参数
科
Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)
属
Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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