Adolescent male and female rats show enhanced latent inhibition of conditioned fear compared to adult rats

Christina Jennifer Perry¹Ricky John²Han B Trinh²Katherine Dawn Drummond²Chun Hui J Park³Jee Hyun Kim^3*

• ¹Macquarie University, Sydney, Australia
• ²The University of Melbourne, Melbourne, Australia
• ³Deakin University, Geelong, Australia

Abstract Latent inhibition is diminished associative memory because of pre-exposure to the conditioned stimulus (CS) without any consequences. Latent inhibition likely plays a significant role in the ontogeny of anxiety disorders, which may explain why anxiety disorders are particularly prevalent in adolescence. Therefore, the present study examined latent inhibition of conditioned fear in adolescent and adult rats of each sex. Given that adolescence is associated with deficits in fear extinction, we hypothesized that latent inhibition is impaired in adolescents compared to adults and expected females to show age-specific estrous cycle effects. On day 1, male (Experiment 1) and female (Experiment 2) rats were placed in fear conditioning chambers. Half of the rats received pre-exposure to the tone cue while the other half received nothing. On day 2, all rats were placed back in the same chambers and exposed to 3 cue-footshock pairings. Latent inhibition was tested on day 3 with 20 presentations of the cue by itself in the same chamber. We unexpectedly observed enhanced latent inhibition in adolescents compared to adults in both male and female rats, indicated by lower levels of freezing due to pre-exposure to the cue. In addition, estrous cycle did not affect latent inhibition at any age. These results suggest that benign experience to a cue reduces subsequent conditioning to the cue more potently in adolescence compared to adulthood, which suggests a potential resilience mechanism naturally occurring in adolescence.