Sex differences in the effects of N-ethylpentylone in young CD1 mice: Insights on behaviour, thermoregulation and early gene expression

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• dc.contributor.author Espinosa Velasco, María
• dc.contributor.author Castro Zavala, Adriana, 1988-
• dc.contributor.author Reguilón, Marina D.
• dc.contributor.author Gallego-Landin, Ines
• dc.contributor.author Bellot, Marina
• dc.contributor.author Rublinetska, Olga
• dc.contributor.author Valverde Granados, Olga
• dc.contributor.author Rodríguez-Arias, Marta
• dc.contributor.author Nadal Gratacós, Núria
• dc.contributor.author Berzosa, Xavier
• dc.contributor.author Gómez Canela, Cristian
• dc.contributor.author Lí Carbó, Marcel
• dc.contributor.author Camarasa, Jorge
• dc.contributor.author Escubedo, Elena
• dc.contributor.author López Arnau, Raúl
• dc.contributor.author Pubill, David
• dc.date.accessioned 2024-09-17T06:23:33Z
• dc.date.available 2024-09-17T06:23:33Z
• dc.date.issued 2024
• dc.description.abstract Background and purpose: New psychoactive substances such as N-ethylpentylone (NEP) are continuously emerging in the illicit drug market, and knowledge of their effects and risks, which may vary between sexes, is scarce. Our present study compares some key effects of NEP in male and female mice. Experimental approach: Psychostimulant, rewarding and reinforcing effects were investigated by tracking locomotor activity, conditioned place preference (CPP) paradigm and through a self-administration (SA) procedure, respectively, in CD1 mice. Moreover, the expression of early genes (C-fos, Arc, Csnk1e, Pdyn, Pp1r1b and Bdnf in addiction-related brain areas) was assessed by qPCR. Finally, serum and brain levels of NEP were determined by UHPLC-MS/MS. Key results: NEP-treated males experimented locomotor sensitisation and showed higher and longer increases in locomotion as well as higher hyperthermia after repeated administration than females. Moreover, while preference score in the CPP was similar in both sexes, extinction occurred later, and reinstatement was more easily established for males. Female mice self-administered more NEP than males at a higher dose. Differences in early gene expression (Arc, Bdnf, Csnk1e and Ppp1r1b) were found, but the serum and brain NEP levels did not differ between sexes. Conclusion and implications: Our results suggest that male mice are more sensitive to NEP psychostimulant and rewarding effects. These differences may be attributed to different early gene expression but not to pharmacokinetic factors. Moreover, males appear to be more vulnerable to the hyperthermic effects of NEP, while females might be more prone to NEP abuse.
• dc.description.sponsorship This work was supported by a grant from Plan Nacional sobre Drogas (ref. n° 2020I051). D.P., R.L-A., M.C., J.C. and E.E. belong to 2021SGR090 and AC-Z, IG-L and OV to 2021SGR00485, both consolidated research groups by Generalitat de Catalunya. I.G-L. is funded with a grant from the Ministerio de Ciencia e Innovación (PRE2020-091923). The Department of Medicine and Health Sciences (UPF) is a “Unidad de Excelencia María de Maeztu”, funded by the Agencia Estatal de Investigación (#CEX2018-000792-M). O.V. is recipient of an ICREA Academia Award (Institució Catalana de Recerca i Estudis Avançats, Generalitat de Catalunya).
• dc.format.mimetype application/pdf
• dc.identifier.citation Espinosa-Velasco M, Castro-Zavala A, Reguilón MD, Gallego-Landin I, Bellot M, Rublinetska O, et al. Sex differences in the effects of N-ethylpentylone in young CD1 mice: Insights on behaviour, thermoregulation and early gene expression. Br J Pharmacol. 2024 Nov;181(22):4491-513. DOI: 10.1111/bph.16506
• dc.identifier.doi http://dx.doi.org/10.1111/bph.16506
• dc.identifier.issn 0007-1188
• dc.identifier.uri http://hdl.handle.net/10230/61105
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof Br J Pharmacol. 2024 Nov;181(22):4491-513
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PRE2020-091923
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CEX2018-000792-M
• dc.rights © 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword N‐ethylpentylone
• dc.subject.keyword Addiction
• dc.subject.keyword Ephylone
• dc.subject.keyword New psychoactive substances
• dc.subject.keyword Sex differences
• dc.subject.keyword Synthetic cathinones
• dc.title Sex differences in the effects of N-ethylpentylone in young CD1 mice: Insights on behaviour, thermoregulation and early gene expression
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion