Impaired fear extinction recall in serotonin transporter knockout rats is transiently alleviated during adolescence

Pieter Schipper, Paola Brivio, David De Leest, Leonie Madder, Beenish Asrar, Federica Rebuglio, Michel M.M. Verheij, Tamas Kozicz, Marco A. Riva, Francesca Calabrese, Marloes J.A.G. Henckens, Judith R. Homberg

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Adolescence is a developmental phase characterized by emotional turmoil and coincides with the emergence of affective disorders. Inherited serotonin transporter (5-HTT) downregulation in humans increases sensitivity to these disorders. To reveal whether and how 5-HTT gene variance affects fear-driven behavior in adolescence, we tested wildtype and serotonin transporter knockout (5-HTT-/-) rats of preadolescent, adolescent, and adult age for cued fear extinction and extinction recall. To analyze neural circuit function, we quantified inhibitory synaptic contacts and, through RT-PCR, the expression of c-Fos, brain-derived neurotrophic factor (BDNF), and NDMA receptor subunits, in the medial prefrontal cortex (mPFC) and amygdala. Remarkably, the impaired recall of conditioned fear that characterizes preadolescent and adult 5-HTT-/- rats was transiently normalized during adolescence. This did not relate to altered inhibitory neurotransmission, since mPFC inhibitory immunoreactivity was reduced in 5-HTT-/- rats across all ages and unaffected in the amygdala. Rather, since mPFC (but not amygdala) c-Fos expression and NMDA receptor subunit 1 expression were reduced in 5-HTT-/- rats during adolescence, and since PFC c-Fos correlated negatively with fear extinction recall, the temporary normalization of fear extinction during adolescence could relate to altered plasticity in the developing mPFC.

Original languageEnglish (US)
Article number118
JournalBrain Sciences
Issue number5
StatePublished - May 2019


  • Adolescence
  • Age
  • BDNF
  • Fear extinction
  • Medial prefrontal cortex
  • NMDA
  • Rat
  • Serotonin transporte

ASJC Scopus subject areas

  • Neuroscience(all)


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