Striatal Dopamine D2 Receptors Regulate Cost Sensitivity and Behavioral Thrift

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Molecular Psychiatry

Background:

• The role of dopamine D2 receptors (D2R) in appetitive behavior is debated, with conflicting theories on its effect on motivation and overeating.
• Previous research suggests D2R signaling influences motivated behaviors, but its precise function in cost-benefit analyses of foraging remains unclear.

Purpose of the Study:

• To investigate the role of dopamine D2 receptors (D2R) in regulating effort-based foraging behavior.
• To differentiate between the effects of D2R blockade and genetic deletion on motivated behavior and energy expenditure.

Main Methods:

• Utilized a homecage foraging paradigm in mice to assess behavior following haloperidol administration (D2R antagonist).
• Generated and studied mice with selective genetic deletion of D2R in indirect pathway medium spiny neurons (iMSNs).
• Assessed foraging strategy, consumption, body weight, sucrose preference, and reinforcement.

Main Results:

• Haloperidol administration shifted foraging strategy towards less effortful food pursuit without altering consumption or body weight.
• Selective D2R deletion in iMSNs reduced effort and energy expenditure in food pursuit, leading to weight loss, especially under escalating costs.
• D2R deletion did not affect sucrose preference or reinforcement, indicating D2R's role is in effort regulation, not primary motivation or reward.

Conclusions:

• Striatal D2R is critical for regulating behavioral effort and cost sensitivity in foraging.
• Reduced D2R signaling diminishes effort and energy expenditure, suggesting it may contribute to reduced physical activity in obesity rather than increased overeating.