Dual role of dopamine D2-like receptors in the mediation of conditioned and unconditioned fear

Marcus Lira Brandão, Amanda Ribeiro De Oliveira, Sangu Muthuraju, Ana Caroline Colombo, Viviane Mitsuko Saito, Teddy Talbot

Research output: Contribution to journalReview articlepeer-review

24 Scopus citations


A reduction of dopamine release or D2 receptor blockade in the terminal fields of the mesolimbic system, particularly the amygdala, clearly reduces conditioned fear. Similar D2 receptor antagonism in the neural substrates of fear in the midbrain tectum attenuates the processing of unconditioned aversive information. However, the implications of the interplay between opposing actions of dopamine in the rostral and caudal segments of the dopaminergic system are still unclear. Previous studies from this laboratory have reported the effects of dopaminergic drugs on behavior in rats in the elevated plus maze, auditory-evoked potentials (AEPs) recorded from the midbrain tectum, fear-potentiated startle, and conditioned freezing. These findings led to an interesting framework on the functional roles of dopamine in both anxiety and fear states. Dopamine D2 receptor inhibition in the terminal fields of the mesolimbic dopamine system generally causes anxiolytic-like effects, whereas the activity of midbrain substrates of unconditioned fear are enhanced by D2 receptor antagonists, suggesting that D2 receptor-mediated mechanisms play opposing roles in fear/anxiety processes, depending on the brain region under study. Dopamine appears to mediate conditioned fear by acting at rostral levels of the brain and regulate unconditioned fear at the midbrain level, likely by reducing the sensorimotor gating of aversive events.

Original languageEnglish (US)
Pages (from-to)3433-3437
Number of pages5
JournalFEBS Letters
Issue number22
StatePublished - Jan 20 2015


  • Anxiety
  • Brain aversion system
  • Conditioned fear
  • Dopamine
  • Panic
  • Unconditioned fear

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


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