Early-life stress exacerbates the effects of WIN55,212-2 and modulates the cannabinoid receptor type 1 expression

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• dc.contributor.author Martín Sánchez, Ana
• dc.contributor.author García Baos, Alba
• dc.contributor.author Castro Zavala, Adriana, 1988-
• dc.contributor.author Alegre Zurano, Laia
• dc.contributor.author Valverde Granados, Olga
• dc.date.accessioned 2022-01-20T07:06:41Z
• dc.date.available 2022-01-20T07:06:41Z
• dc.date.issued 2021
• dc.description.abstract Early-life stress induces an abnormal brain development and increases the risk of psychiatric diseases, including depression, anxiety and substance use disorders. We have developed a reliable model for maternal neglect, named maternal separation with early weaning (MSEW) in CD1 mice. In the present study, we evaluated the long-term effects on anxiety-like behaviours, nociception as well as the Iba1-positive microglial cells in this model in comparison to standard nest (SN) mice. Moreover, we investigated whether MSEW alters the cannabinoid agonist WIN55,212-2 effects regarding reward, spatial and emotional memories, tolerance to different cannabinoid responses, and physical dependence. Adult male offspring of MSEW group showed impaired responses on spatial and emotional memories after a repeated WIN55,212-2 treatment. These behavioural impairments were associated with an increase in basolateral amygdala and hippocampal CB1-expressing fibres and higher number of CB1-containing cells in cerebellum. Additionally, MSEW promotes a higher number of Iba1-positive microglial cells in basolateral amygdala and cerebellum. As for the cannabinoid-induced effects, rearing conditions did not influence the rewarding effects of WIN55,212-2 in the conditioned place preference paradigm. However, MSEW mice showed a delay in the development of tolerance to the cannabinoid effects. Moreover, CB1-positive fibres were reduced in limbic areas in MSEW mice after cannabinoid withdrawal precipitated with the CB1 antagonist SR141617A. These findings support that early-life stress promotes behavioural and molecular changes in the sensitivity to cannabinoids, which are mediated by alterations in CB1 signalling in limbic areas and it induces an increased Iba1-microglial marker which could interfere in emotional memories formation.
• dc.description.sponsorship This study was supported by the Ministerio de Economia y Competitividad (grant number SAF2016-75966-R-FEDER and PID2019-104077RB-100), Ministerio de Sanidad (Retic-ISCIII, RD16/017/010 and Plan Nacional sobre Drogas 2018/007). L.A.Z received a FPI grant (BES-2017-080066) from Ministerio de Economia y Competitividad. A.G-B received a FI-AGAUR grant from the Generalitat de Catalunya (2019FI_B0081). A.C-Z received CONACYT grant (276577) from the Mexican government.
• dc.format.mimetype application/pdf
• dc.identifier.citation Martín-Sánchez A, García-Baos A, Castro-Zavala A, Alegre-Zurano L, Valverde O. Early-life stress exacerbates the effects of WIN55,212-2 and modulates the cannabinoid receptor type 1 expression. Neuropharmacology. 2021;184:108416. DOI: 10.1016/j.neuropharm.2020.108416
• dc.identifier.doi http://dx.doi.org/10.1016/j.neuropharm.2020.108416
• dc.identifier.issn 0028-3908
• dc.identifier.uri http://hdl.handle.net/10230/52266
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Neuropharmacology. 2021;184:108416
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-75966-R
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-104077RB-100
• dc.rights © Elsevier http://dx.doi.org/10.1016/j.neuropharm.2020.108416
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword Cannabinoid receptor type 1
• dc.subject.keyword Iba1
• dc.subject.keyword Maternal separation
• dc.subject.keyword Memory
• dc.subject.keyword Physical dependence
• dc.subject.keyword WIN55,212-2
• dc.title Early-life stress exacerbates the effects of WIN55,212-2 and modulates the cannabinoid receptor type 1 expression
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion