Dopaminergic modulation of schema-dependent learning

Background Long-term memory for novel information can be supported by presenting it within a known semantic context. This so-called congruency effect has long been described as an example for schema-dependent learning, but the underlying neural mechanisms still remain unclear. Therefore, we tested the hypothesis that dopamine plays a critical role through the regulation of prefrontal and mesolimbic brain regions. Methods In a double-blind between-subjects design, 90 healthy humans (70 female, 30 male) received either a dopamine agonist (1.25 mg bromocriptine), a dopamine antagonist (400 mg sulpiride), or a placebo before the encoding of semantically congruent and incongruent words, while their brain activity was scanned using fMRI. Results Behaviorally, semantic congruency enhanced recognition memory on the next day in all three groups, and this effect was modulated by drug following an inverted U-shaped function. Specifically, the congruency effect was highest under placebo and significantly reduced by both the agonist and antagonist. On the neural level, subsequent memory effects for congruent items in the left inferior frontal gyrus and its connectivity with the left substantia nigra and right nucleus accumbens, respectively, were also modulated by drug in a quadratic fashion, although to a lesser degree. Conclusion Our findings give novel insights by showing that schema-dependent learning is modulated by dopamine and they suggest that this could relate to prefrontal and interconnected mesolimbic regions.