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Title: | Repeated administration of N-ethyl-pentedrone induces increased aggression and impairs social exploration after withdrawal in mice |
Author: | Espinosa-Velasco, María Reguilón, Marina D. Bellot, Marina Nadal-Gratacós, Núria Berzosa, Xavier Gómez-Canela, Cristian Rodríguez-Arias, Marta Camarasa García, Jordi Escubedo Rafa, Elena Pubill Sánchez, David López Arnau, Raúl |
Keywords: | Drogues Estimulants Agressivitat Drugs of abuse Stimulants Aggressiveness |
Issue Date: | 13-Jul-2022 |
Publisher: | Elsevier B.V. |
Abstract: | N-ethyl-pentedrone (NEPD, 2-(ethylamino)-1-phenyl-1-pentanone) is one of the latest synthetic cathinone derivatives that emerged into the illicit drug market. This drug has psychostimulant properties and has been related with several intoxications and even fatalities. However, information about the consequences of its acute and repeated consumption is lacking. Thus, the aim of our study was to investigate the behavioral effects after both acute and repeated NEPD exposure as well as the neurochemical changes. Male OF1 mice were treated with an acute dose (1, 3 or 10 mg/kg, i.p.) or received repeated injections of these doses (twice/day, 5 days) of NEPD. Shortly after drug-exposure or during drug-withdrawal, anxiety-like behavior, aggressiveness, social interaction, depressive-like symptoms, body weight and temperature were assessed. Also, monoamine synthesis enzymes, levels of neurotransmitters and their precursors and main metabolites, as well as ΔFosB, were determined in striatum and prefrontal cortex from post-mortem tissue. Acute administration of NEPD induced anxiolytic effects and reduced social exploration whereas during withdrawal after repeated administration the anxiolytic effect had vanished, and the reduced social exploration was still present and accompanied with increased aggressive behavior. Moreover, NEPD (10 mg/kg) induced slight hyperthermia and reduced weight gain during the repeated administration, whereas increased locomotor activity and lack of depressive symptoms were found during withdrawal. This was accompanied by increased plasma corticosterone and decrease in striatal dopamine. Finally, the long-lasting and robust increase in ΔFosB levels found in striatum after NEPD chronic exposure suggests a high risk of dependence. The increased aggressivity and locomotor activity, together with this potential of inducing dependence justify a warning about the risks of consumption of NEPD if translated to humans. Keywords: Addiction; Aggressive behavior; Monoamine levels; N-ethyl-pentedrone; Synthetic cathinones. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.pnpbp.2022.110562 |
It is part of: | Progress in Neuro-Psychopharmacology & Biological Psychiatry, 2022, vol. 117 |
URI: | http://hdl.handle.net/2445/195590 |
Related resource: | https://doi.org/10.1016/j.pnpbp.2022.110562 |
ISSN: | 0278-5846 |
Appears in Collections: | Articles publicats en revistes (Institut de Biomedicina (IBUB)) Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) |
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