7,8-dihydroxyflavone, a TrkB receptor agonist, blocks long-term spatial memory impairment caused by immobilization stress in rats.
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.
Institute of Neurosciences, Autonomous University of Barcelona, Bellaterra 08193, Barcelona, Spain.
Raül
R
Andero
Núria
N
Daviu
Rosa Maria
RM
Escorihuela
Roser
R
Nadal
Antonio
A
Armario
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003345:Corticosterone / Q000097:blood; D044950:Flavanones / Q000494:pharmacology* / Q000627:therapeutic use; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000819:agonists* / Q000378:metabolism; D012149:Restraint, Physical; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism / Q000503:physiopathology; D013312:Stress, Physiological / Q000502:physiology*; D013315:Stress, Psychological / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology
C478869:7,8-dihydroxyflavanone; D044950:Flavanones; D000324:Adrenocorticotropic Hormone; D020813:Receptor, trkB; D003345:Corticosterone