Behavioural and neurochemical effects after repeated administration of N‐ethylpentylone (ephylone) in mice

Abstract

N‐ethyl‐pentylone (NEP), also known as ‘ephylone’ and N‐ethylnorpentylone, has been identified as one of the most recent novel psychostimulants to emerge into the illicit drug market and it has been associated with some intoxications and even fatalities. However, little is known about the consequences of its repeated consumption as well as the role of the monoaminergic system in such consequences. Thus, the aim of our study was to investigate the neurochemical profile and the behavioural effects after both acute and repeated NEP exposure. Male OF1 mice were acutely (1, 3, 10 mg/kg, i.p.) or repeatedly (1, 3, 10 mg/kg, i.p., 5 days, twice/day) exposed to NEP, and anxiety‐like behaviour, aggressiveness, social interaction, depressive‐like symptoms, body temperature, changes in monoaminergic enzymes and neurotransmitters levels as well as ΔFosB in striatum and prefrontal cortex (PFC) from post‐mortem tissue were analysed short after drug‐exposure or during drug‐withdrawal. Acute administration of NEP induced anxiolytic effects but also an aggressive behaviour and social exploration deficits in mice, which persist during NEP‐withdrawal. Moreover, NEP induced hyperthermia as well as depressive‐like symptoms after repeated administrations that may be related to the decrease in serotonin and noradrenaline levels observed in striatum and PFC. Finally, the long‐term increase in ΔFosB levels in striatum after NEP chronic exposure points to a high risk of dependence. Altogether indicates that NEP consumption induces different neurological and neuropsychiatric disorders accompanied by changes in the monoaminergic system, posing a threat to public health.

A review of synthetic cathinones emerging in recent years (2019–2022)

“…In rats, ephylone showed locomotor stimulant effects similar to methamphetamine, but was less potent than it and showed a shorter duration of action [137,138]. In addition, repeated administration of ephylone caused anxiolytic-like and depressive-like effects and aggressiveness in rats [138,139]. Studies in rodents suggest that ephylone has a high addictive potential [137,[139][140][141].…”

“…In addition, repeated administration of ephylone caused anxiolytic-like and depressive-like effects and aggressiveness in rats [138,139]. Studies in rodents suggest that ephylone has a high addictive potential [137,[139][140][141]. Additionally, studies in zebrafish showed its neurotoxicity, cardiotoxicity and developmental toxicity [142].…”