Regulation of Fear Extinction in the Basolateral Amygdala by Dopamine D2 Receptors Accompanied by Altered GluR1, GluR1-Ser845 and NR2B Levels

Abstract

The amygdala, a critical structure for both Pavlovian fear conditioning and fear extinction, receives sparse but comprehensive dopamine innervation and contains dopamine D1 and D2 receptors. Fear extinction, which involves learning to suppress the expression of a previously learned fear, appears to require the dopaminergic system. The specific roles of D2 receptors in mediating associative learning underlying fear extinction require further study. Intra-basolateral amygdala (BLA) infusions of a D2 receptor agonist, quinpirole, and a D2 receptor antagonist, sulpiride, prior to fear extinction and extinction retention were tested 24 h after fear extinction training for long-term memory (LTM). LTM was facilitated by quinpirole and attenuated by sulpiride. In addition, A-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor glutamate receptor 1 (GluR1) subunit, GluR1 phospho-Ser845, and N-methyl-D-aspartic acid receptor NR2B subunit levels in the BLA were generally increased by quinpirole and down-regulated by sulpiride. The present study suggests that activation of D2 receptors facilitates fear extinction and that blockade of D2 receptors impairs fear extinction, accompanied by changes in GluR1, GluR1-Ser845 and NR2B levels in the amygdala.

Dopamine neurons drive fear extinction learning by signaling the omission of expected aversive outcomes

“…Plasticity in the amygdala and IL underlie acquisition and consolidation of fear extinction memories ( Duvarci and Pare, 2014 ; Maren et al, 2013 ; Pape and Pare, 2010 ; Sotres-Bayon and Quirk, 2010 ; Tovote et al, 2015 ). Furthermore, DA signaling in the amygdala and IL has been shown to play an important role in fear extinction ( Abraham et al, 2014 ; Haaker et al, 2013 ; Hikind and Maroun, 2008 ; Mueller et al, 2010 ; Shi et al, 2017 ; Whittle et al, 2016 ). Interestingly, optogenetic inhibition of DA neurons during US omission has been found to prevent extinction-related plasticity in the amygdala and IL ( Luo et al, 2018 ).…”

A dopaminergic switch for fear to safety transitions

“…In mammalian systems, separable populations of dopamine neurons project to the NAc, amygdala and mPFC 16 and distinct calcium changes have been reported in different VTA-dopamine terminal fields 17 , 18 . Importantly, dopamine receptor activation in the vmPFC, amygdala and NAc modulates extinction learning and memory 19 – 23 . This suggests that based on their projection targets, distinct subpopulations of dopamine neurons may differentially regulate fear extinction.…”

Social Company by a Receptive Mating Partner Facilitates Fear Extinction

“…A growing literature indicates that dopamine plays an important role in fear extinction (Abraham et al, 2014). A previous study reported that activation of D2 receptors facilitates fear extinction and that blockade of D2 receptors impairs fear extinction (Shi et al, 2017). Furthermore, a blockade of the D1 receptor in the BLA before an extinction session disrupted fear extinction (Hikind and Maroun, 2008).…”