The “highs and lows” of the human brain on dopaminergics: Evidence from neuropharmacology

•Drug manipulation of dopaminergic neurotransmission is a valuable tool to understand the role of dopamine in reward processing.•We systematically reviewed all studies examining effects of dopaminergic drug manipulation on human neurobehavioral responses to reward.•Inter-individual variables influence neurobehavioral reward correlates after dopaminergic drug manipulation and should be considered.•We provide systematized knowledge to inform the design of future studies and rational therapeutic models targeting reward dysfunction.

Rewards are appetitive events that elicit approach. Ground-breaking findings from neurophysiological experiments in animals, alongside neuropharmacology and neuroimaging research in human samples have identified dopamine as the main neurochemical messenger of global reward processing in the brain. However, dopamine's contribution to the different components of reward processing remains to be precisely defined. To facilitate the informed design and interpretation of reward studies in humans, we have systematically reviewed all existing human pharmacological studies investigating how drug manipulation of the dopamine system affects reward-related behaviour and its neural correlates. Pharmacological experiments in humans face methodological challenges in terms of the: 1) specificity and safety of the available drugs for administration in humans, 2) uncertainties about pre- or post-synaptic modes of action, and 3) possible interactions with inter-individual neuropsychological or genotypic variables. In order to circumvent some of these limitations, future research should rely on the combination of different levels of observation, in integrative pharmaco-genetics-neurobehavioral approaches, to more completely characterize dopamine's role in both general and modality-specific processing of reward.