Stress‐induced escalation of alcohol self‐administration, anxiety‐like behavior, and elevated amygdala Avp expression in a susceptible subpopulation of rats

Abstract

Comorbidity between alcohol use and anxiety disorders is associated with more severe symptoms and poorer treatment outcomes than either of the conditions alone. There is a well‐known link between stress and the development of these disorders, with post‐traumatic stress disorder as a prototypic example. Post‐traumatic stress disorder can arise as a consequence of experiencing traumatic events firsthand and also after witnessing them. Here, we used a model of social defeat and witness stress in rats, to study shared mechanisms of stress‐induced anxiety‐like behavior and escalated alcohol self‐administration. Similar to what is observed clinically, we found considerable individual differences in susceptibility and resilience to the stress. Both among defeated and witness rats, we found a subpopulation in which exposure was followed by emergence of increased anxiety‐like behavior and escalation of alcohol self‐administration. We then profiled gene expression in tissue from the amygdala, a key brain region in the regulation of stress, alcohol use, and anxiety disorders. When comparing “comorbid” and resilient socially defeated rats, we identified a strong upregulation of vasopressin and oxytocin, and this correlated positively with the magnitude of the alcohol self‐administration and anxiety‐like behavior. A similar trend was observed in comorbid witness rats. Together, our findings provide novel insights into molecular mechanisms underpinning the comorbidity of escalated alcohol self‐administration and anxiety‐like behavior.

Repeated ethanol exposure following avoidance conditioning impairs avoidance extinction and modifies conditioning‐associated prefrontal dendritic changes in a mouse model of post‐traumatic stress disorder

“…This mouse finding is in accordance with other recent rodent data, showing that pronounced effects of ethanol characterise animals expressing maladaptive behavioural responses to stress. These effects were observed either with the CPP paradigm (Bahi & Dreyer, 2014; Bahi & Dreyer, 2020; Macedo et al, 2018; Yu et al, 2016), with the two‐bottle free choice paradigm (Cannady et al, 2021; Manjoch et al, 2016; Meyer et al, 2013) or with the self‐administration paradigm (Barchiesi et al, 2021; Edwards et al, 2013; Makhijani et al, 2021). Nevertheless, studies with other drugs (such as cocaine and methamphetamine) have shown that stress does not necessarily lead to potentiate the effect of the drug or increase its consumption (e.g., cocaine: Enman et al, 2015; Hadad et al, 2016; Lguensat et al, 2021; methamphetamine: Eagle & Perrine, 2013).…”

Mice Cohabiting With Familiar Conspecific in Chronic Stress Condition Exhibit Methamphetamine-Induced Locomotor Sensitization and Augmented Consolation Behavior

“…Thus, despite not being deeply explored, psychological stress may cause drug abuse-like behaviors similar to those who experienced stress directly. For instance, studies demonstrated increased rewarding effects of cocaine and alcohol in animals that witnessed chronic defeat stress applied to their cagemates ( Garcia-Carachure et al, 2020 ; Barchiesi et al, 2021 ). However, no studies have verified the consequences of vicarious stress in drug-induced locomotor sensitization.…”

Ethanol intake in male mice exposed to social defeat: Environmental enrichment potentiates resilience

“…With regard to ethanol, exposure to SD increases the conditioned rewarding effects of ethanol using the CPP paradigm ( Macedo et al, 2018 ). Studies of voluntary ethanol consumption have observed increased and escalating consumption of ethanol, as well as an increased motivation to drink alcohol, in defeated animals using the oral SA paradigm ( Barchiesi et al, 2021 ; Montagud-Romero et al, 2021 ; Norman et al, 2015 ; Reguilón et al, 2020 , 2021 ; Rodríguez-Arias et al, 2016 ). Using other paradigms such as the two-bottle choice, an increase in SD-induced escalation of alcohol intake has also been observed ( Croft et al, 2005 ; Deal et al, 2018 ; Hwa et al, 2016 ; Newman et al, 2018a ).…”