Chinese researchers have reported that adolescent stress affects adult behavior response strategy, and N-Methyl-D-aspartic (NMDA) receptors, a type of glutamate receptors, in the dorsolateral striatum (DLS) may play an essential role in this effect.

Led by Dr. ZHANG Jianjun from the Institute of Psychology of the Chinese Academy of Sciences (CAS), the researchers found that adolescent chronic unpredictable stress (CUS) causes a bias to goal-directed behavior and the down-regulation of N-methyl-D-aspartate receptor subtype 2B (NR2B) in the DLS in adult rats.

In daily life, when facing conventional problems, we will use the habitual behavior system to improve efficiency in order not to occupy more cognitive resources of the brain. However, in unfamiliar situations, individuals need to switch to the goal-oriented behavior system and consciously adjust their behavior to adapt to changes in the environment flexibly. Habitual behavior triggers behavior through stimulus-response linkages. It is formed after the many successive occurrences of stimuli and behaviors.

On the other hand, goal-directed behaviors are sensitive to the outcome of an action. If the outcome does not meet the current needs, the individual will quickly adjust the behavior pattern. Under normal circumstances, when individuals make behavioral responses, their goal-oriented strategy and habitual strategy can be closely coordinated and flexibly switched according to changes in the external environment. Accumulating evidence indicates that exposure to CUS in adulthood affects the bias between goal-directed and habitual strategies.

Adolescence is a transitional period from childhood to adulthood that lays the foundation for behavior and performance in adulthood. The brain undergoes structural and functional remodeling during adolescence, increasing vulnerability to environmental stress. Adolescent stress is a risk factor for many habit-related psychiatric disorders, including obesity, addiction, and Parkinson's disease. However, how adolescent stress affects behavior response strategy is still elusive.

In the current study, rats are divided into two groups and exposed to CUS during early adolescence or middle adolescence respectively. The researchers trained the rats to earn the sucrose pellets reward with a nose poke a hole in the chambers when the rats reach adulthood. Different schemes for obtaining sucrose pellets can distinguish goal-directed behavior from habitual behavior.

After training, the outcome devaluation test was operated to test whether the rats, after pre-feeding, still nose-poke the hole without sucrose pellets reward. If not, it meant sucrose pellets are less valuable to rats, and the behavior is goal-oriented.

The researchers reported middle adolescent CUS, but not early adolescent CUS exposure, led rats to favor goal-directed strategy rather than habitual strategy in adulthood. As habitual strategy consumes low attention and energy, the result may imply insufficient adaptability and unnecessary cognitive resources in adulthood after CUS exposure in middle adolescence.

Previous studies indicate that adolescent stress may influence the expression of NMDA receptor and dopamine receptor in the DLS and dorsomedial striatum (DMS). Research further evaluated the level of NMDA receptor subtype 2 A (NR2A), NR2B (the subunits of the NMDA receptor), dopamine D1 receptor (D1R), and dopamine D2 receptor (D2R) in the DLS and DMS after stress treatment by simple western blotting based on a capillary electrophoresis technology system.

They found that rats stressed in middle adolescence showed a significantly lower level of NR2B in DMS relative to controls, while there were no differences of any other receptors subunits of rats stressed in early adolescence, suggesting the potential role of NR2B in DLS in the regulation of the abnormal habitual behaviors induced by adolescent stress.

This study provides new insights in establishing middle adolescence as a key "development window" in the stress effects on instrumental behavior in adulthood. In addition, it sheds light on the neural mechanisms underlying this stress effect.

This work was published in Developmental Psychobiology and was supported by the CAS-VPST Silk Road Science Fund 2021.