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7,8‐dihydroxyflavone, a TrkB receptor agonist, blocks long‐term spatial memory impairment caused by immobilization stress in rats
Author(s) -
Andero Raül,
Daviu Núria,
Escorihuela Rosa Maria,
Nadal Roser,
Armario Antonio
Publication year - 2012
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.20906
Subject(s) - memory impairment , morris water navigation task , tropomyosin receptor kinase b , psychology , long term potentiation , hippocampal formation , hippocampus , agonist , neuroscience , neurotrophic factors , brain derived neurotrophic factor , water maze , medicine , receptor , cognition
Post‐traumatic stress disorder (PTSD) patients show cognitive deficits, but it is unclear whether these are a consequence of the pathology or a pre‐existing factor of vulnerability to PTSD. Animal models may help to demonstrate whether or not exposure to certain stressors can actually induce long‐lasting (LL; days) impairment of hippocampus‐dependent memory tasks and to characterize neurobiological mechanisms. Adult male rats were exposed to 2‐h immobilization on boards (IMO), a severe stressor, and spatial learning in the Morris water maze (MWM) was studied days later. Exposure to IMO did not modify learning or short‐term memory in the MWM when learning started 3 or 9 days after IMO, but stressed rats did show impaired long‐term memory at both times, in accordance with the severity of the stressor. New treatments to prevent PTSD symptoms are needed. Thus, considering the potential protective role of brain‐derived neurotrophic factor (BDNF) on hippocampal function, 7,8‐dihydroxyflavone (7,8‐DHF), a recently characterized agonist of the BDNF receptor TrkB, was given before or after IMO in additional experiments. Again, exposure to IMO resulted in LL deficit in long‐term memory, and such impairment was prevented by the administration of 7,8‐DHF either 2 h prior IMO or 8 h after the termination of IMO. The finding that IMO‐induced impairment of spatial memory was prevented by pharmacological potentiation of TrkB pathway with 7,8‐DHF even when the drug was given 8 h after IMO suggests that IMO‐induced impairment is likely to be a LL process that is strongly dependent on the integrity of the BDNF‐TrkB system and is susceptible to poststress therapeutic interventions. 7,8‐DHF may represent a new therapeutic approach for early treatment of subjects who have suffered traumatic experiences. © 2010 Wiley Periodicals, Inc.