Effects of juvenile exposure to predator odor on adolescent and adult anxiety and pain nociception

Abstract

Clinical researchers have tracked patients with early life trauma and noted generalized anxiety disorder, unipolar depression, and risk-taking behaviors developing in late adolescence and into early adulthood. Animal models provide an opportunity to investigate the neural and developmental processes that underlie the relationship between early stress and later abnormal behavior. The present model used repeated exposure to 2,3,5-trimethyl-3-thiazoline (TMT), a component of fox feces, as an unconditioned fear-eliciting stimulus in order to induce stress in juvenile rats aged postnatal day (PND) 23 through 27. After further physical maturation characteristic of the adolescent stage (PND 42), animals were tested using an elevated plus maze (EPM) for anxiety and plantar test (Hargreaves method) for pain to assess any lingering effects of the juvenile stress. To assess how an additional stress later in life affects anxiety and pain nociception, PND 43 rats were exposed to inescapable shock (0.8 mA) and again tested on EPM and plantar test. A final testing period was conducted in the adult (PND 63) rats to assess resulting changes in adult behaviors. TMT-exposed rats were significantly more anxious in adolescence than controls, but this difference disappeared after exposure to the secondary stressor. In adulthood, but not in adolescence, TMT-exposed rats demonstrated lower pain sensitivity than controls. These results suggest that early life stress can play a significant role in later anxiety and pain nociception, and offer insight into the development and manifestation of anxiety- and trauma-related disorders.

Changes in dam and pup behavior following repeated postnatal exposure to a predator odor (TMT): A preliminary investigation in long‐evans rats

“…Recent work has investigated the effect of prolonged postnatal predator odor exposure on future learning, memory, anxiety, and defensive behaviors (Chen, Shen, Liu, & Li, ; Kenny, Wright, Green, Mashoodh, & Perrot, ; Mashoodh, Sinal, & Perrot‐Sinal, ; Post, Dahlborg, O'Loughlin, & Bloom, ). Mashoodh and colleagues found that rats repeatedly exposed to cat odor from PN1‐21 decreased their suppression of grooming over time and exhibited changes in corticosterone secretion across sexes (Mashoodh, Wright, Hebert, & Perrot‐Sinal, ).…”

“…Recent work has investigated the effect of prolonged postnatal predator odor exposure on future learning, memory, anxiety, and defensive behaviors (Chen, Shen, Liu, & Li, 2014;Kenny, Wright, Green, Mashoodh, & Perrot, 2014;Mashoodh, Sinal, & Perrot-Sinal, 2009;Post, Dahlborg, O'Loughlin, & Bloom, 2014).…”

How Animal Models Inform Child and Adolescent Psychiatry

“…4–6 Physical changes can be introduced in odors or in surrounding objects. 5,7 The social environment can be modified through maternal care or aggressive cage-mates. 8,9 Behavioral experience is a complex form of manipulation that involves altered environments.…”

“…Altered experience such as a more or less enriched environment or learning of other kinds is particularly important when considering development interaction. 7 …”

Endogenous Estrogen Influences Predator Odor-Induced Impairment of Cognitive and Social Behaviors in Aromatase Gene Deficiency Mice

“…Various animal models have been developed for the investigations of dramatic stress. Predator odor fears conditioning is one of the most common models for the investigation of dramatic stress in rodents [ 7 , 8 ], while many other models are also employed to investigate the maternal separation [ 9 ], immobilization stress [ 10 ], restraint stress [ 11 ], and drug stimulation [ 12 ] in various studies. 2,3,5-Trimethyl-3-thiazoline (TMT), a sulfur-containing odor isolated from fox feces [ 13 ], is one of the most widely used predator odor stressor.…”