Dopamine D3 Receptor Availability Is Associated with Inflexible Decision Making

Area of Science:

• Neuroscience
• Behavioral Science
• Pharmacology

Background:

• Dopamine D2/3 receptor signaling is crucial for adaptive behaviors.
• The specific role of D3 receptors in decision-making and reinforcement learning remains unclear.

Purpose of the Study:

• To investigate the role of dopamine D3 receptors in flexible decision-making and reinforcement learning.
• To examine individual differences in D3 receptor availability and their impact on behavior.

Main Methods:

• Positron Emission Tomography (PET) with [(11)C]-(+)-PHNO to quantify D3 receptor availability in rats.
• A three-choice spatial acquisition and reversal-learning task with probabilistic reinforcement.
• Pharmacological administration of a D3-preferring agonist and computational modeling of choice behavior.

Main Results:

• Midbrain [(11)C]-(+)-PHNO binding negatively correlated with adaptation to changing rewarded locations during reversal learning.
• D3 receptor availability was linked to learning rate and sensitivity to positive feedback, but not negative feedback.
• D3 receptor availability and agonist administration impaired reversal performance by reducing learning rate and positive feedback sensitivity.

Conclusions:

• Dopamine D3 receptors play a previously unrecognized role in specific aspects of reinforcement learning and flexible decision-making.
• Individual variations in midbrain D3 receptor availability influence adaptive behavior.
• These findings implicate the dopamine D3 receptor in decision-making processes relevant to psychiatric disorders.