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. (2nd November 2021)

• Record Type: Journal Article
• Authors: Lguensat, Asmae; Boudjafad, Zineb; Giorla, Elodie; Bennis, Mohamed; Baunez, Christelle; Garcia, René; Ba‐M'hamed, Saadia
• Is Part Of: European journal of neuroscience. Volume 54:Number 10(2021)
• Page Start: 7710
• Page End: 7732
• Publication Date: 2021-11-02
• Subjects: avoidance extinction impairment -- ethanol exposure -- mice -- PTSD‐like phenotype; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.15499
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: Treatment of post‐traumatic stress disorder is complicated by the presence of alcohol use disorder comorbidity. Little is known about the underlying brain mechanisms. We have recently shown, in mice, that the post‐traumatic stress disorder‐like phenotype is characterised by the increase and decrease in total dendritic number and length in the prelimbic and infralimbic areas of the medial prefrontal cortex, respectively. Here, we examined whether repeated ethanol exposure would exacerbate these changes and whether this would be associated with difficulty to extinguish passive avoidance behaviour, as an indicator of treatment resistance. We also analysed whether other known trauma‐associated changes, like increased or decreased corticosterone and decreased brain‐derived neurotrophic factor levels, would also be exacerbated. Male mice underwent trauma exposure (1.5‐mA footshock), followed, 8 days later, by a conditioned place preference training with ethanol. Tests for fear sensitization, passive avoidance, anxiety‐like behaviour, extinction acquisition and relapse susceptibility were used to assess behaviour changes. Plasma corticosterone and brain‐derived neurotrophic factor levels and prefrontal dendritic changes were subsequently measured. Trauma‐susceptible mice exposed to ethanol acquired a strong place preference and behaved differently from those not exposed to ethanol, with delayed avoidance extinction and higher avoidance relapse vulnerability. Ethanol potentiated trauma‐associated dendritic changes in the prelimbic area and suppressed trauma‐associated dendritic changes in the infralimbic area. However, ethanol had no effect on trauma‐induced increased corticosterone and decreased brain‐derived neurotrophic factor levels. These data suggest that the modification of prefrontal trauma‐related changes, due to alcohol use, can characterise, and probably support, treatment‐resistant post‐traumatic stress disorder. Abstract : Ethanol exposure (ip injections at the dose of 1.6 g/kg, during a conditioned place preference training that was performed 8 days following trauma with a high intensity, 1.5 mA, footshock) altered avoidance extinction and increased susceptibility to avoidance relapse. It also provoked an increase in total dendritic number and length in the prelimbic area of the medial prefrontal cortex. A positive correlation was found between susceptibility to avoidance relapse and changes in both dentritic parameters in the prelimbic area.