Chronic intranasal oxytocin reverses stress-induced social avoidance in female prairie voles.

Social anxiety disorder (SAD) is a prevalent mental illness in both men and women, but current treatment approaches with selective serotonin reuptake inhibitors (SSRI) have limited success. The neuropeptide oxytocin (OXT) has become a therapeutic target due to its prosocial and anxiolytic effects. Nevertheless, no research has focused on the impact of chronic OXT treatment in animal models of SAD. Social defeat stress is an animal model of social conflict that reliably induces a social avoidance phenotype, reflecting symptoms observed in individuals suffering from SAD. Here, we used the socially monogamous prairie vole, which exhibits aggressive behavior in both sexes, to examine the effects of OXT and SSRI treatment following social defeat stress in males and females. Defeated voles became avoidant in unfamiliar social situations as early as one day after defeat experience, and this phenotype persisted for at least eight weeks. OXT receptor (OXTR) binding in mesocorticolimbic and paralimbic regions was reduced in defeated females during the eight-week recovery period. In males, serotonin 1A receptor binding was decreased in the basolateral amygdala and dorsal raphe nucleus starting at one week and four weeks post-defeat, respectively. Chronic intranasal treatment with OXT had a negative effect on sociability and mesolimbic OXTR binding in non-defeated females. However, chronic intranasal OXT promoted social engagement and increased mesolimbic OXTR binding in defeated females but not males. SSRI treatment led to only modest effects. This study identifies a sex-specific and stress-dependent function of intranasal OXT on mesolimbic OXTR and social behaviors.

Regulation of defeat-induced social avoidance by medial amygdala DRD1 in male and female prairie voles.

Social interaction with unfamiliar individuals is necessary for species-preserving behaviors such as finding mates and establishing social groups. However, social conflict is a potential negative outcome to interaction with a stranger that can be distressing enough to cause an individual to later avoid interactions with other unfamiliar conspecifics. Unfortunately, stress research using a prominent model of social conflict, social defeat stress, has largely omitted female subjects. This has left a void in the literature regarding social strain on female stress biology and adequate comparison of the effect of sex in stress pathways. The prairie vole (Microtus ochrogaster) exhibits aggressive behavior in both sexes, making voles an attractive candidate to model social defeat in both sexes. This study sought to establish a model of social defeat stress in both male and female prairie voles, characterize behavioral changes in response to this stressor, and investigate the role of dopamine signaling in the response to social defeat stress. Defeated male and female prairie voles displayed social avoidance as well as an increase in the level of dopamine receptor D1 (DRD1) in the medial amygdala (MeA). Pharmacological manipulation of DRD1 signaling in the MeA revealed that increased DRD1 signaling is sufficient to induce a social avoidant state, and could be a necessary component in the defeat-induced social avoidance response. These findings provide the prairie vole as a model of social defeat in both sexes, and implicate the MeA in avoidance of unfamiliar conspecifics after a distressing social encounter.

Delay discounting as impaired valuation: Delayed rewards in an animal obesity model.

Obesity is a major public health problem, which, like many forms of addiction, is associated with an elevated tendency to choose smaller immediate rather than larger delayed rewards, a response pattern often referred to as excessive delay discounting. Although some accounts of delay discounting conceptualize this process as impulsivity (placing the emphasis on overvaluing the smaller immediate reward), others have conceptualized delay discounting as an executive function (placing the emphasis on delayed rewards failing to retain their value). The present experiments used a popular animal model of obesity that has been shown to discount delayed rewards at elevated rates (i.e., obese Zucker rats) to test two predictions that conceptualize delay discounting as executive function. In the first experiment, acquisition of lever pressing with delayed rewards was compared in obese versus lean Zucker rats. Contrary to predictions based on delay discounting as executive function, obese Zucker rats learned to press the lever more quickly than controls. In the second experiment, progressive ratio breakpoints (a measure of reward efficacy) with delayed rewards were compared in obese versus lean Zucker rats. Contrary to the notion that obese rats fail to value delayed rewards, the obese Zucker rats' breakpoints were (at least) as high as those of the lean Zucker rats.