Dopamine D 2-like receptors modulate freezing response, but not the activation of HPA axis, during the expression of conditioned fear

Exp Brain Res. 2017 Feb;235(2):429-436. doi: 10.1007/s00221-016-4805-3. Epub 2016 Oct 20.


Considering the complexity of aversive information processing and defensive response expression, a combined action of stress modulators may be required for an optimal performance during threatening situations. Dopamine is now recognized as one of the most active modulators underlying states of fear and anxiety. On the other hand, activation of hypothalamic-pituitary-adrenocortical (HPA) axis, which leads to the release of corticosterone in rodents, has been considered a key part of the stress response. The current study is an extension of prior work investigating modulatory effects of dopamine and corticosterone on conditioned fear expression. We have showed that corticosterone, acting through mineralocorticoid receptors in the ventral tegmental area (VTA), upregulates dopaminergic system in the basolateral amygdala (BLA), enabling the expression of conditioned freezing response. The novel question addressed here is whether VTA-BLA dopaminergic signaling is necessary for increases in corticosterone during conditioned fear expression. Using site-specific treatment with D2-like agonist quinpirole (VTA) and D2-like antagonist sulpiride (BLA), we evaluated freezing and plasma corticosterone in rats exposed to a light used as aversive conditioned stimulus (CS). Intra-VTA quinpirole and intra-BLA sulpiride significantly decreased freezing expression in the conditioned fear test, but this anxiolytic-like effect of the dopaminergic drugs was not associated with changes in plasma corticosterone concentrations. Altogether, data suggest that interferences with the ability of the CS to activate the dopaminergic VTA-BLA pathway reduce the expression of freezing, but activation of the HPA axis seems to occur upstream of the recruitment of dopaminergic mechanisms in conditioned fear states.

Keywords: Basolateral amygdala; Corticosterone; Dopamine; Fear conditioning; Freezing; Ventral tegmental area.

MeSH terms

  • Amygdala / drug effects
  • Amygdala / physiology
  • Animals
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology*
  • Corticosterone / metabolism
  • Dopamine / pharmacology
  • Dopamine Agents / pharmacology
  • Fear / drug effects
  • Fear / physiology*
  • Freezing Reaction, Cataleptic / drug effects
  • Freezing Reaction, Cataleptic / physiology*
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / physiology
  • Male
  • Microinjections
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / physiology
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D2 / metabolism*
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / physiology


  • Dopamine Agents
  • Receptors, Dopamine D2
  • Dopamine
  • Corticosterone