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Licensed Unlicensed Requires Authentication Published by De Gruyter September 4, 2018

Understanding the role of dopamine in conditioned and unconditioned fear

  • Marcus L. Brandão EMAIL logo and Norberto C. Coimbra


Pharmacological and molecular imaging studies in anxiety disorders have primarily focused on the serotonin system. In the meantime, dopamine has been known as the neurotransmitter of reward for 60 years, particularly for its action in the nervous terminals of the mesocorticolimbic system. Interest in the mediation by dopamine of the well-known brain aversion system has grown recently, particularly given recent evidence obtained on the role of D2 dopamine receptors in unconditioned fear. However, it has been established that excitation of the mesocorticolimbic pathway, originating from dopaminergic (DA) neurons from the ventral tegmental area (VTA), is relevant for the development of anxiety. Among the forebrain regions innervated by this pathway, the amygdala is an essential component of the neural circuitry of conditioned fear. Current findings indicate that the dopamine D2 receptor-signaling pathway connecting the VTA to the basolateral amygdala modulates fear and anxiety, whereas neural circuits in the midbrain tectum underlie the expression of innate fear. The A13 nucleus of the zona incerta is proposed as the origin of these DA neurons projecting to caudal structures of the brain aversion system. In this article we review data obtained in studies showing that DA receptor-mediated mechanisms on ascending or descending DA pathways play opposing roles in fear/anxiety processes. Dopamine appears to mediate conditioned fear by acting at rostral levels of the brain and regulate unconditioned fear at the midbrain level.


The research was supported by FAPESP (process no. 2016/04620-1, Funder Id: 10.13039/501100001807) and CNPq (process no. 02651/2014-4).

  1. Conflict of interest

  2. The authors have no conflicts of interest to declare.


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Received: 2018-03-16
Accepted: 2018-06-10
Published Online: 2018-09-04
Published in Print: 2019-04-24

©2019 Walter de Gruyter GmbH, Berlin/Boston

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