The BDNF receptor TrkB is critical to the acquisition but not expression of conditioned incentive value

摘要

Stimuli paired with reward acquire incentive properties that are important for many aspects of motivated behavior, such as feeding and drug-seeking. Here we used a novel chemical-genetic strategy to determine the role of the BDNF receptor TrkB, known to be critical to many aspects of neural development and plasticity, during acquisition and expression of positive incentive value to a cue paired with food. We assessed that cue's learned incentive value in a conditioned reinforcement task, in which its ability to reinforce instrumental responding later, in the absence of food itself, was examined. In TrkB^F616A knock-in mice, TrkB-kinase activity was suppressed by administering the TrkB inhibitor 1NMPP1 during the period of initial cue incentive learning only (i.e., Pavlovian training), during nose-poke conditioned reinforcement testing only, during both phases, or neither phase. All mice acquired cue-food associations as indexed by approach responses. However, TrkB^F616A mice that received 1NMPP1 during initial cue incentive learning failed to show conditioned reinforcement of nose-poking regardless of their treatment in testing, whereas administration of 1NMMP1 only during the testing phase had no effect. The effects of 1NMPP1 administration were due to inhibition of TrkB^F616A because performance of wild-type mice was unaffected by administration of the compound during either phase. These data indicate that BDNF signaling through TrkB receptors is required for the acquisition of positive incentive value, but is not needed to express previously-acquired incentive value in the reinforcement of instrumental behavior.