Influence of footshock number and intensity on the behavioral and endocrine response to fear conditioning and cognitive fear generalization in male rats

Foot-shock paradigms have provided valuable insights into the neurobiology of stress and fear conditioning. An extensive body of literature indicates that shock exposure can elicit both conditioned and unconditioned effects, although delineating between the two is a challenging task. This distinction holds crucial implications not only for the theoretical interpretation of fear conditioning, but also for properly evaluating putative preclinical models of post-traumatic stress disorder (PTSD) involving shock exposure. The characteristics of shocks (intensity and number) affect the strength of learning, but how these characteristics interact to influence conditioned and unconditioned consequences of shocks are poorly known. In this study, we aimed to investigate in adult male rats the impact of varying shock number and intensity on the endocrine and behavioral response to contextual fear conditioning and fear generalization to a novel environment markedly distinct from the shock context (i.e., fear generalization). Classical biological markers of stress (i.e., ACTH, corticosterone, and prolactin) were sensitive to manipulations of shock parameters, whereas these parameters had a limited effect on contextual fear conditioning (evaluated by freezing and distance traveled). In contrast, behavior in different novel contexts (fear generalization) was specifically sensitive to shock intensity. Notably, altered behavior in novel contexts markedly improved, but not completely normalized after fear extinction, hypoactivity apparently being the result of both conditioned and unconditioned effects of foot-shock exposure. The present results will contribute to a better understanding of shock exposure as a putative animal model of PTSD.