The effects of dopaminergic D2-like receptor stimulation upon behavioral and neural correlates of renewal depend on individual context processing propensities

Renewal is defined as the recovery of an extinguished response when the contexts of extinction and recall differ. Prominent hippocampal activity during context-related extinction can predict renewal. Dopaminergic antagonism during extinction learning impaired extinction and reduced hippocampal activation, without affecting renewal. However, to what extent dopaminergic stimulation during extinction influences hippocampal processing and renewal is as yet unknown. In this fMRI study, we investigated the effects of the dopamine D2-like agonist bromocriptine upon renewal in an associative learning task, in hippocampus and ventromedial PFC. We observed significant differences between bromocriptine (BROMO) and placebo (PLAC) treatments in the subgroups showing (REN) and lacking (NoREN) renewal: the renewal level of BROMO REN was significantly higher, and associated with more prominent hippocampal activation during extinction and recall, compared to PLAC REN and BROMO NoREN. Results suggest that an interaction between D2like-agonist-induced enhancement of hippocampal activity and a pre-existing tendency favoring context processing contributed to the higher renewal levels. In contrast, ventromedial prefrontal activation was unchanged, indicating that increased hippocampal context processing and not prefrontal response selection constituted the central driving force behind the high renewal levels. The findings demonstrate that hippocampal dopamine is important for encoding and providing of context information, and thus crucially involved in the renewal effect.