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Stress is a critical factor in the development of mental disorders such as addiction, underscoring the importance of stress resilience strategies. While the ketogenic diet (KD) has shown efficacy in reducing alcohol consumption in male mice without cognitive impairment, its impact on the stress response and addiction development, especially in females, remains unclear. This study examined the KD's effect on increasing ethanol intake due to vicarious social defeat (VSD) in female mice. Sixty-four female OF1 mice were divided into two dietary groups: standard diet (n = 32) and KD (n = 32). These were further split based on exposure to four VSD or exploration sessions, creating four groups: EXP-STD (n = 16), VSD-STD (n = 16), EXP-KD (n = 16), and VSD-KD (n = 16). KD-fed mice maintained ketosis from adolescence until the fourth VSD/EXP session, after which they switched to a standard diet. The Social Interaction Test was performed 24 h after the last VSD session. Three weeks post-VSD, the Drinking in the Dark test and Oral Ethanol Self-Administration assessed ethanol consumption. The results showed that the KD blocked the increase in ethanol consumption induced by VSD in females. Moreover, among other changes, the KD increased the expression of the ADORA1 and CNR1 genes, which are associated with mechanisms modulating neurotransmission. Our results point to the KD as a useful tool to increase resilience to social stress in female mice. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Stress is one of the main risk factors that can induce humans to develop disorders such as depression, anxiety, or drug use. One of the main sources of stress is social interaction, which can lead to situations like bullying at school or work. In this article we will review the close relationship between exposure to stressful situations and increased cocaine or alcohol use. We will also present the main results obtained with animal models, which have allowed researchers to study the brain mechanisms involved in the impact of stress on drug use. To conclude, we will detail the main mechanisms that explain the powerful effect that stress has on substance use. [ABSTRACT FROM AUTHOR]