Dopaminergic modulation of reward discounting in healthy rats: a systematic review and meta-analysis

Castrellon, J. J. and Meade, J. and Greenwald, L. and Hurst, K. and Samanez-Larkin, G. R.

Psychopharmacology (Berl) (2021) 238: 711–723

DOI: 10.1007/s00213-020-05723-5

Abstract

RATIONALE: Although numerous studies have suggested that pharmacological alteration of the dopamine (DA) system modulates reward discounting, these studies have produced inconsistent findings. OBJECTIVES: Here, we conducted a systematic review and pre-registered meta-analysis to evaluate DA drug-mediated effects on reward discounting of time, probability, and effort costs in studies of healthy rats. This produced a total of 1343 articles to screen for inclusion/exclusion. From the literature, we identified 117 effects from approximately 1549 individual rats. METHODS: Using random effects with maximum-likelihood estimation, we meta-analyzed placebo-controlled drug effects for (1) DA D1-like receptor agonists and (2) antagonists, (3) D2-like agonists and (4) antagonists, and (5) DA transporter-modulating drugs. RESULTS: Meta-analytic effects showed that DAT-modulating drugs decreased reward discounting. While D1-like and D2-like antagonists both increased discounting, agonist drugs for those receptors had no significant effect on discounting behavior. A number of these effects appear contingent on study design features like cost type, rat strain, and microinfusion location. CONCLUSIONS: These findings suggest a nuanced relationship between DA and discounting behavior and urge caution when drawing generalizations about the effects of pharmacologically manipulating dopamine on reward-based decision-making.

Citation

Castrellon, J. J., Meade, J., Greenwald, L., Hurst, K., & Samanez-Larkin, G. R. (2021). Dopaminergic modulation of reward discounting in healthy rats: a systematic review and meta-analysis. Psychopharmacology (Berl), 238(3), 711–723. https://doi.org/10.1007/s00213-020-05723-5 Animals, Male, Rats, Dose-Response Relationship, Drug, Biological Transport, Meta-analysis, Probability, *Reward, Brain/drug effects/metabolism, Decision Making/*drug effects, Decision-making, Delay, Delay Discounting/*drug effects, Discounting, Dopamine, Dopamine Agonists/*pharmacology, Dopamine Antagonists/*pharmacology, Effort, Pharmacology, Receptors, Dopamine D1/*metabolism, Receptors, Dopamine D2/*metabolism

Keywords

• Animals
• Male
• Rats
• Dose-Response Relationship
• Drug
• Biological Transport
• Meta-analysis
• Probability
• *Reward
• Brain/drug effects/metabolism
• Decision Making/*drug effects
• Decision-making
• Delay
• Delay Discounting/*drug effects
• Discounting
• Dopamine
• Dopamine Agonists/*pharmacology
• Dopamine Antagonists/*pharmacology
• Effort
• Pharmacology
• Receptors
• Dopamine D1/*metabolism
• Receptors
• Dopamine D2/*metabolism