Behavioral Engagement With Playable Objects Resolves Stress-Induced Adaptive Changes by Reshaping the Reward System

Area of Science:

• Neuroscience
• Behavioral Science
• Molecular Biology

Background:

• The reward system regulates motivated behaviors, but the reciprocal mechanisms between behavior and the reward system are not fully understood.
• Chronic stress can lead to depressive-like behaviors, and the underlying neural pathways require further elucidation.

Purpose of the Study:

• To investigate the neural mechanisms by which engagement with playable objects alleviates depressive-like behaviors induced by chronic stress.
• To understand how the reward system is modified by chronic stress and how behavioral interventions can reverse these changes.

Main Methods:

• Utilized chronic restraint stress in mice to induce depressive-like behaviors.
• Employed molecular, pharmacological, genetic, and behavioral analyses, including microarray, liquid chromatography, and chemogenetics.
• Examined the roles of dopamine, PACAP, and dopamine receptors (D1 and D2) in the nucleus accumbens-lateral shell (NAc-lSh) and its circuits.

Main Results:

• Chronic stress caused dopamine surges and PACAP upregulation in the NAc-lSh, facilitating depressive-like behaviors.
• Engagement with playable objects normalized dopamine responses, reduced PACAP upregulation, and ameliorated depressive-like behaviors.
• Dopamine D1 receptor overactivation in NAc-lSh promoted depression, while D1 inhibition or PACAP upregulation conferred resilience.

Conclusions:

• Behavioral engagement with playable objects reverses stress-induced depressive-like behaviors by resolving maladaptive changes in the reward system.
• The study highlights the plasticity of reward circuitry and its role in stress resilience.