The activation of D2-like receptors by intranasal dopamine facilitates the extinction of contextual fear and prevents conditioned fear-induced antinociception

Fear extinction (FExt) is used to treat patients with posttraumatic stress disorder (PTSD). However, fear related to traumatic events can be persistent and return even after successful extinction. The neurochemical control of extinction seems to be performed by several neurotransmitters, including dopamine (DA), through D1 and D2 receptors. Recently, we showed that intranasally applied DA (IN-DA) facilitated the FExt, but the mechanisms by which it promoted this effect are still unknown. This study focused on investigating whether these effects are mediated by the action of DA on D2-like receptors since these receptors seem to be related to neurochemical and molecular changes underlying extinction. Also, we investigated whether IN-DA treatment would affect conditioned fear-induced antinociception (Fear-IA). Rats treated with IN-DA (1 mg/kg) twenty-five minutes after sulpiride (SUL; 40 mg/kg, i.p., D2-antagonist) were subjected to the extinction of contextual fear. IN-DA applied before the extinction session induced the FExt and prevented Fear-IA. These effects were impaired by pretreatment with SUL, suggesting that the IN-DA effects are mediated by DA on D2-like receptors. SUL per se also facilitated the FExt but did not affect Fear-IA. These data suggest IN-DA as a promising pharmacological tool to supplement the psychotherapy of patients suffering from PTSD.

Automated summary

Fear extinction (FExt) is used for patients with PTSD, but fear can persist. The study investigated the role of DA on D2 receptors in promoting FExt, and the effects of IN-DA on conditioned fear-induced antinociception. IN-DA showed potential as a pharmacological tool for PTSD therapy.