Anti-inflammatory agents for smoking cessation? Focus on cognitive deficits associated with nicotine withdrawal in male mice

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  • dc.contributor.author Saravia Santos, Rocio, 1988-
  • dc.contributor.author Ten-Blanco, Marc
  • dc.contributor.author Grande, María T.
  • dc.contributor.author Maldonado, Rafael, 1961-
  • dc.contributor.author Berrendero Díaz, Fernando, 1971-
  • dc.date.accessioned 2019-01-15T08:05:49Z
  • dc.date.issued 2019
  • dc.description.abstract Nicotine withdrawal is associated with cognitive deficits including attention, working memory, and episodic memory impairments. These cognitive deficits are a hallmark of nicotine abstinence which could be targeted in order to prevent smoking relapse. The underlying mechanisms, however, are poorly understood. In this study, memory impairment was observed in mice 4 days after the precipitation of nicotine withdrawal by the nicotinic antagonist mecamylamine. The presence of cognitive deficits correlated with microglial activation in the hippocampus and the prefrontal cortex. Moreover, an increased expression of neuroinflammatory markers including IL1β, TNFα and IFNγ was found in both memory-related brain regions. Notably, flow cytometric analysis also revealed an enhancement of TNFα and IFNγ plasmatic levels at the same time point during nicotine withdrawal. Impaired neurogenesis, as shown by reduction in the expression of the endogenous cell proliferation marker Ki67 and the early neuron marker doublecortin, was also associated with nicotine abstinence. Treatment with the non-psychoactive cannabinoid cannabidiol abolished memory impairment of nicotine withdrawal and microglia reactivity, reduced the expression of IL1β and IFNγ in the hippocampus and the prefrontal cortex, respectively, and normalized Ki67 levels. The nonsteroidal anti-inflammatory drug indomethacin also prevented cognitive deficits and microglial reactivity during withdrawal. These data underline the usefulness of anti-inflammatory agents to improve cognitive performance during early nicotine abstinence.
  • dc.description.sponsorship This work was supported by “Plan Nacional sobre Drogas”(#2014I019) and “Ministerio de Economía y Competitividad” MINECO/FEDER, UE (SAF2017-85299-R) to FB, the “Generalitat deCatalunya-AGAUR” (#2014-SGR-1547), ICREA-Acadèmia (2015) and “Ministerio de Economía y Competitividad” (#SAF2017-84060-R) to RM. Rocio Saraviais a recipient of a predoctoral fellowship from the “Instituto de Salud Carlos III”
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Saravia R, Ten-Blanco M, Grande MT, Maldonado R, Berrendero F. Anti-inflammatory agents for smoking cessation? Focus on cognitive deficits associated with nicotine withdrawal in male mice. Brain Behav Immun. 2019 Jan;75:228-39. DOI: 10.1016/j.bbi.2018.11.003
  • dc.identifier.doi http://dx.doi.org/10.1016/j.bbi.2018.11.003
  • dc.identifier.issn 0889-1591
  • dc.identifier.uri http://hdl.handle.net/10230/36267
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.ispartof Brain, behavior, and immunity. 2019 Jan;75:228-39
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2017-84060-R
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2017-85299-R
  • dc.rights © Elsevier http://dx.doi.org/10.1016/j.bbi.2018.11.003
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.subject.other Nicotina -- Addicció
  • dc.subject.other Memòria
  • dc.subject.other Microglia -- Reactivitat
  • dc.subject.other Indometacina
  • dc.subject.other Citocines
  • dc.subject.other Cannabidiol
  • dc.title Anti-inflammatory agents for smoking cessation? Focus on cognitive deficits associated with nicotine withdrawal in male mice
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/acceptedVersion