Bidirectional changes in water-maze learning following recombinant adenovirus-associated viral vector (rAAV)-mediated brain-derived neurotrophic factor expression in the rat hippocampus

Susanna Pietropaolo, Jean Charles Paterna, Hansruedi Büeler, Joram Feldon, Kay Yan Benjamin Yee

Research output: Journal article publicationJournal articleAcademic researchpeer-review

14 Citations (Scopus)


Alterations in hippocampal brain-derived neurotrophic factor (BDNF) expression have been implicated in the pathogenesis of emotional and cognitive dysfunction. Here, we induced BDNF overexpression in the rat hippocampus using recombinant adenovirus-associated viral (rAAV) vectors, and studied its long-term (2 months postinduction) effects on anxiety-related behaviour, exploration in the open field, and spatial learning in the water maze. Although the treatment successfully led to substantial elevation of hippocampal BDNF levels, its effect on spatial learning was bidirectional: a subset of rAAV-induced BDNF-overexpressing rats performed well above control level, whereas the rest were clearly impaired. This behavioural distinction corresponded to two markedly different levels of BDNF overexpression. The increase in dorsal hippocampal BDNF content achieved in the 'water-maze- impaired' subgroup was twice that attained in the 'water-maze-improved' rats. Although neither subgroup of rAAV-induced BDNF-overexpressing rats differed from controls in the open field, the 'water-maze-impaired' subgroup also showed a significant anxiolytic effect. Our results suggest that hippocampal BDNF elevation significantly affects cognitive and emotional behaviours, but the direction and magnitude of the effects critically depend on the precise levels of overexpression. This factor must be taken into account in future studies examining the functional consequences of hippocampal BDNF overexpression.
Original languageEnglish
Pages (from-to)533-547
Number of pages15
JournalBehavioural Pharmacology
Issue number5-6
Publication statusPublished - 1 Sep 2007
Externally publishedYes


  • Anxiety
  • Brain-derived neurotrophic factor
  • Learning
  • Open field
  • Rat

ASJC Scopus subject areas

  • Pharmacology
  • Neuroscience(all)

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