Enhancement of response learning in male rats with intrastriatal infusions of a BDNF -TrkB agonist, 7,8-dihydroxyflavone.

Cognitive and physical activity modulate learning and memory across many different paradigms and contexts. Enhancement of learning and memory by cognitive and physical exercise may be mediated by brain-derived neurotrophic factor (BDNF) acting at tropomyosin receptor kinase B (TrkB). Upregulation of BDNF and systemic administration of a TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), improves cognition in rodents. These actions have largely been shown in studies using drug administration for days to months and models to reverse impairments in learning and memory largely using hippocampus-sensitive tasks. The present study determined whether a single intrastriatal infusion of 7,8-DHF given near the time of training would enhance learning and memory regulated by striatal function in cognitively intact rats. We examined the acute effects of intrastriatal infusions of 7,8-DHF (1, 5, and 10 μg/0.5 μl DMSO) on striatum-sensitive response learning and on phosphorylation of TrkB receptors in male rats. All doses of 7,8 DHF improved learning in the response maze compared to vehicle controls. In untrained rats, intrastriatal infusions of 7,8-DHF phosphorylated TrkB receptors, suggesting that 7,8-DHF acted as a TrkB agonist and BDNF mimic. The findings that a single, intrastriatal infusion of 7,8-DHF 20 min before training enhanced response learning in rats suggest that, in addition to its trophic effects, BDNF modulates cognition through receptor-mediated cell signaling events at the time of learning.