Neuroactivational and Behavioral Correlates of Psychosocial Stress-Induced Cocaine Seeking in Rats

A prominent feature of cocaine abuse is a high risk of relapse even despite prolonged periods of abstinence. Psychosocial stress is thought to be a major contributor to the onset of cocaine craving and relapse in human substance abusers, yet most preclinical models of stress-induced relapse employ physical stressors (e.g., unpredictable footshock) or pharmacological stressors (e.g., yohimbine to elicit a drug seeking response) and do not rely upon psychosocial stress per se. Importantly, social stressors are well known to activate distinct neural circuits within the brain as compared to other stressors. It is therefore possible that currently available animal models of stress-induced drug relapse do not fully engage the neuroanatomical, neurochemical, and/or molecular substrates that are recruited specifically by psychosocial stressors to produce drug-seeking behavior. Social defeat stress has been proposed as an ethologically valid psychosocial stressor in rodents that more closely models the forms of psychosocial stress that precede relapse episodes in drug abusers. We previously developed a model of psychosocial stress-induced reinstatement in rats in which cocaine seeking is elicited via exposure to a cue signaling impending social defeat stress. Using this model, we discovered that predilection towards displaying active coping behaviors during prior social defeat stress exposures was positively correlated with levels of psychosocial stress-induced cocaine seeking. The present study aimed to expand upon these initial findings by assessing and comparing patterns of neural activation in key brain areas during stress induced cocaine seeking that is triggered by psychosocial or footshock stress predictive cues