A history of chronic adolescent stress attenuates cued fear-potentiated startle in adult female Wistar rats

Post-traumatic stress disorder (PTSD) is a stress and trauma-related disorder that is largely characterized by hyperarousal to fear-based cues. N-methyl-D-aspartate (NMDA) receptors are key mediators of fear learning behaviors. Altered NMDA receptor signaling is a hallmark of PTSD pathology that impacts fear memory learning and extinction processes. In the current study, we observed that exposing adolescent rats to a mixed modality stress paradigm of repeated restraint, social defeat, and individual housing (chronic adolescent stress; CAS) decreases immunoreactivity of the NMDA subunit NR2B in the central amygdala in adulthood. We sought to determine the impact of a peripherally administered NMDA agonist D-cycloserine (DCS) intervention to enhance extinction of learned fear in CAS animals. Upon reaching adulthood, CAS animals were exposed to a cued fear-potentiated startle paradigm. DCS was administered immediately following the first of two extinction sessions with the goal of enhancing the extinction learning. CAS females expressed blunted cued fear conditioning compared to non-stressed females, but were not influenced by the DCS intervention. DCS may have reconsolidated cued fear associations in CAS males, however, males generally were able to successfully learn fear extinction regardless of stress history. These data suggest that chronic stress during adolescence modifies NMDA receptor expression, but functional impacts on cued fear learning differ by sex and require additional approaches to better understand the mechanisms underlying stress-induced impairments in fear learning behaviors.