Dopamine and Reward Systems

Goals

• Discuss dopamine systems in the brain.
• Explore different dopamine receptor types and their drug targeting.
• Examine the affective/limbic loop of the basal ganglia.
• Investigate predictive reward signals and reinforcement learning.
• Introduce decision neuroscience.
• Delve into valuation and the role of the ventromedial prefrontal cortex (vmPFC).

Key Topics and Concepts

Dopamine Overview

• Definition: Dopamine is a catecholamine neuromodulator produced by ~400,000–600,000 neurons in the midbrain.
• Major Pathways:
  1. Nigrostriatal Pathway: Substantia nigra → Dorsal striatum (critical for motor control; implicated in Parkinson’s disease).
  2. Mesolimbic Pathway: Ventral tegmental area (VTA) → Ventral striatum (nucleus accumbens, critical for reward and motivation).
  3. Mesocortical Pathway: VTA → Prefrontal cortex (cognitive control, valuation).
• Mechanisms of Action:
  • Volume transmission influences broad areas.
  • Dopamine receptors are metabotropic, with two main families:
    • D1-like (D1, D5): Excitatory.
    • D2-like (D2, D3, D4): Inhibitory.
• Drug Targets: Many drugs (e.g., L-dopa, MAO inhibitors, cocaine) modulate dopamine synthesis, breakdown, reuptake, or receptor activity.

Motivated Behavior and Reward

• Homeostatic Drives: Dopamine underpins behaviors related to acquiring food, water, warmth, and mating.
• Distinction Between Wanting and Liking:
  • Wanting: Motivated behavior driven by dopamine systems.
  • Liking: Hedonic value associated with opioid systems (not dopamine).
• Examples: Hypothalamic circuits regulate hunger signals (e.g., ghrelin, leptin) and interface with dopamine systems for reward-seeking.

Historical Foundations

• James Olds and Self-Stimulation:
  • Discovery of the “pleasure center” via the medial forebrain bundle.
  • Rats self-stimulated to exhaustion when electrodes stimulated mesolimbic dopamine pathways.
  • Modern applications include deep brain stimulation for treatment-resistant depression.

Reward Prediction and Learning

• Reward Prediction Error (RPE): Pioneered by Wolfram Schulz.
  • Dopamine signals unexpected rewards (positive RPE) or absence of expected rewards (negative RPE).
  • RPE underpins reinforcement learning by adjusting future behaviors based on outcomes.
• Conditioned Stimuli: Dopamine signals shift from the reward itself to predictive cues, facilitating anticipatory behaviors.

Valuation and Decision Neuroscience

• vmPFC and OFC Roles:
  • Encode subjective reward value during decision-making.
  • Strongly connected to the amygdala and striatum.
  • Studies show neurons fire relative to the value of chosen rewards in economic tasks.
• Human Studies: Monetary Incentive Delay (MID) task reveals vmPFC and nucleus accumbens activation during reward anticipation and receipt.

Clinical and Behavioral Implications

• Abulia: Basal ganglia lesions disrupt motivational circuits, leading to lack of initiative despite preserved external responsiveness.
• Drug Addiction: Many substances exploit dopamine pathways, creating reinforcement that overrides homeostatic drives.

Key Terms

• Catecholamine: Class of neurotransmitters including dopamine, norepinephrine.
• Mesolimbic Pathway: Dopamine route central to reward and motivation.
• Volume Transmission: Dopamine diffusion affecting broad neural areas.
• Reward Prediction Error (RPE): Discrepancy between expected and actual rewards.
• vmPFC: Ventromedial prefrontal cortex, critical for valuation and decision-making.
• Self-Stimulation: Behavior driven by direct brain reward system activation.
• Wanting vs. Liking: Distinction between motivational drive (dopamine) and pleasure (opioid systems).

Reading and References

• Primary Text: Principles of Neuroscience, Chapter 32 (focus on Box 32A).
• Key Studies:
  • Schultz, W. (1998). Reward prediction errors in dopaminergic neurons.
  • Olds, J., & Milner, P. (1954). Self-stimulation in rats.

This summary captures the flow and key highlights from the lecture corpus.