Sex-dependent effects of acute stress in adolescence or adulthood on appetitive motivation

Psychopharmacology (Berl). 2024 May 16. doi: 10.1007/s00213-024-06587-9. Online ahead of print.

Abstract

Rationale: Intensely stressful experiences can lead to long-lasting changes in appetitive and aversive behaviors. In humans, post-traumatic stress disorder increases the risk of comorbid appetitive disorders including addiction and obesity. We have previously shown that an acute stressful experience in adult male rats suppresses motivation for natural reward.

Objectives: We examine the impact of sex and age on the effects of intense stress on action-based (instrumental) and stimulus-based (Pavlovian) motivation for natural reward (food).

Methods: Rats received 15 unsignaled footshocks (stress) in a single session followed by appetitive training and testing in a distinct context. In Experiment 1, stress occurred in either adolescence (PN28) or adulthood (PN70) with appetitive training and testing beginning on PN71 for all rats. In Experiment 2, stress and appetitive training/testing occurred in adolescence.

Results: Acute stress in adolescent females suppressed instrumental motivation assessed with progressive ratio testing when testing occurred in late adolescence or in adulthood, whereas in males stress in adolescence did not suppress instrumental motivation. Acute stress in adulthood did not alter instrumental motivation. In contrast, Pavlovian motivation assessed with single-outcome Pavlovian-to-instrumental transfer (SO-PIT) was consistently enhanced in females following adolescent or adult stress. In males, however, stress in adolescence had no effect, whereas stress in adulthood attenuated SO-PIT.

Conclusions: Acute stress in adolescence or adulthood altered instrumental motivation and stimulus-triggered Pavlovian motivation in a sex and developmentally specific manner. These findings suggest that the persistent effects of acute stress on Pavlovian and instrumental motivational processes differ in females and males, and that males may be less vulnerable to the deleterious effects of intense stress during adolescence on appetitive motivation.

Keywords: Adolescence; Development; Instrumental motivation; Pavlovian-to-instrumental transfer; Post-traumatic stress disorder; Sex differences; Stress-enhanced fear learning.