7,8-Dihydroxyflavone Facilitates the Consolidation of Reward-Related Learning Open Access

Liang, Zhijia (2013)

Permanent URL: https://etd.library.emory.edu/concern/etds/08612n911?locale=en



Extensive research has been conducted to elucidate the role of Brain-Derived Neurotrophic Factor (BDNF) secretion and TrkB activation on a myriad of behavioral functions such as fear acquisition and consolidation, as well as morphological changes involved in neuroplasticity of key regions such as the hippocampus, cerebral cortex, and basal forebrain. However, most prior research focused on the effects of BDNF action in an aversive setting, and few studies have examined BDNF action in an appetitive context. As such, we utilized the BDNF analogue 7,8-dihydroxyflavone (7,8-DHF) and systemic administration of the agent to explore the effects of TrkB activation on appetitive conditioning. After acquisition of an instrumental response, mice undergoing reversal training showed evidence of strengthening of consolidation of response-outcome learning after 7,8-DHF treatment, as indicated by increased preference for the previously reinforced aperture. This effect was selective to reinforced responding since 7,8-DHF had no effects on response extinction. We also found that dendritic spine density in the orbito-prefrontal cortex (oPFC), a key area involved in response-outcome conditioning, was increased after 7,8-DHF treatment. Tracing studies also identified the existence of cortico-striatal projections in mice. Together, the data suggest distributed TrkB activation enhances consolidation of response-outcome contingency conditioning, and that the oPFC may be a critical neural substrate. Systemic 7,8-DHF administration may thus serve as a novel treatment option for disorders associated with deficiencies in reward-related learning.

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Table of Contents


Methods and Materials...6

Results...11 Discussion...14

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