ArticlePsychopharmacology2021
Rottlerin, BDNF, and the impairment of inhibitory avoidance memory.
Article in Psychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 9 citations in OpenAlex.
- Enhancement of response learning in male rats with intrastriatal infusions of a BDNF -TrkB agonist, 7,8-dihydroxyflavone.Behavioural brain research · 2026Article
- Differential effects of cannabidiol on inhibitory avoidance memory reconsolidation and consolidation are associated with distinct hippocampal proBDNF and BDNF signaling profiles.Frontiers in neuroscience · 2026Article
- Targeting the postsynaptic scaffolding protein PSD-95 enhances BDNF signaling to mitigate depression-like behaviors in mice.Science signaling · 2024Article
- Inhibition of corticosterone synthesis impairs cued water maze consolidation, but it does not affect the expression of BDNF, CK2 and SGK1 genes in dorsal striatum.Frontiers in behavioral neuroscience · 2024Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
RATIONALE AND
objectiveAs a eukaryotic elongation factor 2 kinase (eEF2K) inhibitor and a mitochondrial uncoupler, oncologists have extensively studied rottlerin. Neuroscientists, however, have accumulated scarce data on the role of rottlerin in affective and cognitive functions. Only two prior studies have, respectively, documented its antidepressant-like effect and how it impairs psychostimulant-supported memory. Whether or not rottlerin would affect aversive memory remains unknown. Hence, we sought to investigate the effects of rottlerin on aversive memory in the inhibitory avoidance (IA) task in mice. MATERIALS AND
methodsMale C57BL/6J mice were trained to acquire the IA task. Rottlerin (5 mg/kg, i.p. or 3 μg bilaterally in the hippocampus) or the vehicle was administered before footshock training (acquisition), after footshock training (consolidation), after the memory reactivation (reconsolidation), and before the test (retrieval) in the IA task.
resultsSystemic and intrahippocampal rottlerin impaired the acquisition, consolidation, and retrieval of IA memory, without affecting the reconsolidation process. Rottlerin (5 mg/kg, i.p.) induced a fast-onset and long-lasting increase in the brain-derived neurotrophic factor (BDNF) protein levels in the mouse hippocampus. Systemic injection of 7,8-dihydroxyflavone (7,8-DHF, 30 mg/kg), a BDNF tropomyosin receptor kinase B (TrkB) agonist impaired IA memory consolidation, and treatment with K252a (5 μg/kg), a Trk receptor antagonist, reversed the suppressing effect of rottlerin on IA memory consolidation.
conclusionRottlerin impairs IA memory consolidation through the enhancement of BDNF signaling in the mouse hippocampus. Excessive brain BDNF levels can be detrimental to cognitive function. Rottlerin is likely to affect the original memory-associated neuroplasticity. Thus, it can be combined with exposure therapy to facilitate the forgetting of maladaptive aversive memory, such as post-traumatic stress disorder (PTSD).
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