The behavioral fallout of combined early-life adversity: maternal separation and limited bedding-nesting both increase goal tracking, delay discounting, and impulsive action, and moderate sign-tracking-perseverance associations in rats

Extensive research with rodent models has shown detrimental effects of early-life adversity (ELA) on behavioral (e.g., impulsive behavior, anxiety, and depression) and neurobiological processes (e.g., alterations of neuroendocrine processes and maturation of brain areas). However, heterogeneous methodologies, including types and variations of ELA manipulations could have contributed to inconsistent findings across studies. Maternal separation (MS) and limited bedding/nesting (LBN) are widely implemented rodent ELA protocols. Orso et al. [1] concluded that combined MS and LBN produce consistent and robust effects due to the complementary roles of the two manipulations, which result in a jointly increase of the challenging conditions imposed to both the dam and the offspring. We explored the effects of combined MS-LBN on four processes linked to both ELA and behavioral disorders in later stages of life: Incentive salience of reward cues, and impulsive choice, action, and persistence/perseverance. Incentive salience was assessed with an Autoshaping Pavlovian conditioning task (AUT). Interaction with the extended lever in an operant chamber was measured as sign-tracking (ST) and nose-pokes in the food-delivery location as goal-tracking (GT). ST was used as an indicator of incentive salience. Impulsive choice was assessed using a delay-discounting task (DDT). Preference for a smaller-sooner reward (SS; 1 pellet immediately) over the larger-later reward (LL; 3 pellets after 0 to 16-s delays) was used as a measure of impulsive choice. Impulsive action was assessed with a multiple schedule of reinforcement with long and short Variable Intervals (VI15 s-VI60 s, respectively). Ineffective/excessive responding during each schedule (i.e., low efficiency) was used as a measure of impulsive action. Extinction (EXT) was introduced when steady performance in the multiple schedule was reached. The number of unreinforced lever presses during EXT was used as a measure of behavioral persistence/perseverance. Lastly, a re-test of the DDT assessed consistency and long-term effects of ELA on impulsive choice. Rats with MS-LBN during post-natal days 2-21 (N = 8) and without ELA (N = 8) were exposed to all the behavioral tasks across a span of 18 weeks. As compared to the No-ELA group, MS-LBN rats displayed higher GT during the AUT, higher impulsive choice during test and re-test of the DDT, and less efficient responding during the long-interval schedule of reinforcement (VI60s). Associations between AUT and reinforcement-schedule performance were identified, with ELA moderating the relationship between ST and efficiency during training and persistence/perseverance during extinction.