Adolescent chronic unpredictable stress causes a bias in goal-directed behavior and distinctively changes the expression of NMDA and dopamine receptors in the dorsomedial and dorsolateral striatum in male rats.

The distinct preferences between goal-directed and habit-directed behaviors involve numerous neurodegenerative and psychiatric disorders. Chronic stress during adulthood biases behavior toward habit-oriented strategies. However, it remains to be studied how adolescence, as a stage in which brain regions are still undergoing development, suffering stress will affect this preference. Here, we exposed rats to chronic unpredictable stress (CUS) at PND 21 to PND 33 and PND 34 to PND 47 to examine its effect on sugar pellet-based instrumental behavior in adulthood. We showed that rats exposed to CUS in middle adolescence had a biased goal-directed strategy rather than a habit-oriented strategy in adulthood, whereas CUS exposure in early adolescence did not have this effect. Moreover, middle adolescent CUS caused the downregulation of the N-methyl-d-aspartate receptor subtype 2 B (NR2B) in the dorsolateral striatum (DLS) rather than in the dorsomedial striatum (DMS), whereas no change was observed in NR2A or the dopamine D1 receptor (D1R) or the dopamine D2 receptor (D2R) in the DLS. Together, these findings suggest that CUS in middle adolescence inhibits habitual behavior in adulthood and downregulates the expression of NR2B in DLS, providing new evidence to understand the molecular mechanisms of abnormal habitual behaviors induced by adolescent stress.