The socially enriched environment test: a new approach to evaluate social behavior in a mouse model of social anxiety disorder.

Social anxiety disorder (SAD) is a common anxiety disorder characterized by a marked fear of social situations. Treatments for SAD, including exposure therapy and medication, are not satisfactory for all patients. This has led to the development of several paradigms to study social fear in rodents. However, there are still some social impairments observed in SAD patients that have never been examined in rodent models. Indeed, social situations avoided by SAD patients include not only social interactions but also public performances and being observed by others. Nevertheless, tests used to assess sociability in rodents evaluate mostly social interaction in pairs. Thus, we developed a new test-a socially enriched environment test-that evaluates sociability within a group of three unfamiliar conspecifics in an enriched environment. In this study, we induced a SAD-like behavior (i.e., social fear) in male mice using social fear conditioning (SFC) and then tested social fear using the socially enriched environment test and the three-chamber test. Finally, we tested the effects of fear extinction and acute diazepam treatment in reversing social fear. Results revealed, in conditioned mice, decreased object exploration in proximity to conspecifics, social interaction, and mouse-like object exploration. Extinction training, but not acute diazepam treatment, reversed SFC-induced behavioral changes. These findings demonstrate that the socially enriched environment test provides an appropriate behavioral approach to better understand the etiology of SAD. This test may also have important implications in the exploration of new treatments.

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.

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.