Brain-derived neurotrophic factor expression is increased in the hippocampus of 5-HT(2C) receptor knockout mice

Hippocampus. 2011 Apr;21(4):434-45. doi: 10.1002/hipo.20759.


Several studies have suggested a close interaction between serotonin (5-HT) and BDNF; however, little is known of the specific relationship between BDNF and the 5-HT(2C) receptor. Therefore, in this study we investigated BDNF expression in 5-HT(2C) receptor knockout mice (5-HT(2C) KO). We also assessed functional consequences of any changes in BDNF using a behavioral test battery. Western blot analysis demonstrated a significant 2.2-fold increase in the expression of the mature form of BDNF in 5-HT(2C) KO mice when compared with wild-type controls (WT) in the hippocampus (P = 0.008), but not frontal cortex or striatum. No differences in the expression of the pro-BDNF isoform were found, and the ratio of mature/pro BDNF was significantly increased in 5-HT(2C) KO (P = 0.003). BDNF mRNA expression in the hippocampus was not different between the genotypes. Hence, increased mature BDNF levels in 5-HT(2C) KO hippocampus are most likely due to increased extracellular cleavage rates of pro-BDNF to its mature form. Protein expression of the BDNF receptor, tropomycin-related receptor B (TrkB), was also unchanged in the hippocampus, frontal cortex and striatum. With repeated training in a 10-day win-shift radial arm maze task, 5-HT(2C) KO and WT showed similar decreases of the number of working memory and reference memory errors. In addition, no genotype specific differences were observed for passive or active avoidance learning. 5-HT(2C) KO showed modest locomotor hyperactivity but no differences in tests for anxiety, sensorimotor gating, or depressive-like behaviors; however, in the tail suspension test 5-HT(2C) KO showed significantly reduced climbing (P < 0.05). In conclusion, loss of 5-HT(2C) receptor expression leads to a marked and selective increase in levels of the mature form of BDNF in the hippocampus. Despite this marked increase, 5-HT(2C) KO show only subtle behavioral changes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / physiology
  • Brain-Derived Neurotrophic Factor* / genetics
  • Brain-Derived Neurotrophic Factor* / metabolism
  • Corpus Striatum / metabolism
  • Depression / metabolism
  • Frontal Lobe / metabolism
  • Hippocampus / metabolism*
  • Memory
  • Mice
  • Mice, Knockout
  • Protein Precursors* / genetics
  • Protein Precursors* / metabolism
  • Receptor, Serotonin, 5-HT2C / metabolism*
  • Receptor, trkB / metabolism
  • Serotonin / metabolism


  • Brain-Derived Neurotrophic Factor
  • Protein Precursors
  • Receptor, Serotonin, 5-HT2C
  • brain-derived neurotrophic factor precursor
  • Serotonin
  • Receptor, trkB