Single dose of a dopamine agonist impairs reinforcement learning in humans: behavioral evidence from a laboratory-based measure of reward responsiveness.
BACKGROUND
The dopaminergic system, particularly D2-like dopamine receptors, has been strongly implicated in reward processing. Animal studies have emphasized the role of phasic dopamine (DA) signaling in reward-related learning, but these processes remain largely unexplored in humans.


OBJECTIVE
To evaluate the effect of a single, low dose of a D2/D3 agonist--pramipexole--on reinforcement learning in healthy adults. Based on prior evidence indicating that low doses of DA agonists decrease phasic DA release through autoreceptor stimulation, we hypothesized that 0.5 mg of pramipexole would impair reward learning due to presynaptic mechanisms.


METHODS
Using a double-blind design, a single 0.5-mg dose of pramipexole or placebo was administered to 32 healthy volunteers, who performed a probabilistic reward task involving a differential reinforcement schedule as well as various control tasks.


RESULTS
As hypothesized, response bias toward the more frequently rewarded stimulus was impaired in the pramipexole group, even after adjusting for transient adverse effects. In addition, the pramipexole group showed reaction time and motor speed slowing and increased negative affect; however, when adverse physical side effects were considered, group differences in motor speed and negative affect disappeared.


CONCLUSIONS
These findings show that a single low dose of pramipexole impaired the acquisition of reward-related behavior in healthy participants, and they are consistent with prior evidence suggesting that phasic DA signaling is required to reinforce actions leading to reward. The potential implications of the present findings to psychiatric conditions, including depression and impulse control disorders related to addiction, are discussed.
Pizzagalli
Diego A
DA
Department of Psychology, Harvard University, 1220 William James Hall, 33 Kirkland Street, Cambridge, MA 02138, USA. dap@wjh.harvard.edu
Evins
A Eden
AE
Schetter
Erika Cowman
EC
Frank
Michael J
MJ
Pajtas
Petra E
PE
Santesso
Diane L
DL
Culhane
Melissa
M
D000284:Administration, Oral; D000328:Adult; D000367:Age Factors; D000465:Algorithms; D001245:Association Learning / Q000187:drug effects*; D001519:Behavior / Q000187:drug effects; D052160:Benzothiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D016009:Chi-Square Distribution; D004193:Discrimination Learning / Q000187:drug effects; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009325:Nausea / Q000139:chemically induced; D000077487:Pramipexole; D011930:Reaction Time / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3 / Q000819:agonists*; D012055:Reinforcement Schedule; D012201:Reward; D012737:Sex Factors
D052160:Benzothiazoles; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D000077487:Pramipexole