Role of cytokine and neurotrophic factors in nicotine addiction in the conditioned place preference paradigm

Magda Luciana de Paula Rosa, Caroline Amaral Machado, Bruna da Silva Oliveira, Eliana Cristina de Brito Toscano, Laila Asth, João Luís Vieira Monteiro de Barros, Antônio Lúcio Teixeira, Fabrício A. Moreira, Aline Silva de Miranda

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


The mechanisms involved in the maintenance of cigarette smoking and nicotine reward remain unclear. Immune response might play an important role in this context. Nicotine may induce both central and systemic inflammatory responses as well as changes in the regulation of brain-derived neurotrophic factor (BDNF). The conditioned place preference (CPP) is a method used for the evaluation of nicotine-induced reward, reproducing nicotine-seeking behavior in humans. So far, there are no studies investigating the relationship between neuroinflammation and nicotine-induced CPP. This study aimed to evaluate the levels of inflammatory mediators and neurotrophic factors in key areas of the central nervous system (CNS) of mice subject to nicotine-induced CPP. CPP was induced with an intraperitoneal administration of 0.5 mg/kg of nicotine in male Swiss mice, using an unbiased protocol. Control group received vehicle by the same route. The levels of cytokines, chemokines, and neurotrophic factors were measured using Enzyme-Linked Immunosorbent Assay (ELISA) in the brain after CPP test. As expected, nicotine induced place preference behavior. In parallel, we observed increased peripheral levels of IL-6 and IL-10 alongside increased hippocampal levels of NGF but decreased GDNF in mice treated with nicotine compared to controls. In the striatum, nicotine promoted decrease of IL-1ß, IL-10 and GDNF levels, while the levels of all the mediators were similar between groups in the pre-frontal cortex. Our results provide evidence on the role of cytokines and neurotrophic factors in nicotine-induced CPP in mice.

Original languageEnglish (US)
Article number136235
JournalNeuroscience Letters
StatePublished - Nov 1 2021
Externally publishedYes


  • CPP
  • Inflammation
  • Neurotrophic factors
  • Nicotine
  • Reward

ASJC Scopus subject areas

  • General Neuroscience


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