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.
Highlights
Fear extinction refers to the decrease in conditioned fear responses that occurs with repeated presentation of the unreinforced conditioned fear stimulus (CS) (Milad and Quirk, 2012)
The present study aimed to examine the effects of bilateral intra-basolateral amygdala (BLA) infusion of a D2 receptor agonist, quinpirole, and a D2 receptor antagonist, sulpiride, before extinction training on the long-term memory (LTM) of fear extinction by using the freezing level of rats as an index of fear
To test whether the effects on fear extinction are due to the drugs themselves or to the effects of the drugs combined with extinction, we evaluated a group that received intra-BLA injection of quinpirole while experiencing fear conditioning without extinction
Summary
Fear extinction refers to the decrease in conditioned fear responses that occurs with repeated presentation of the unreinforced conditioned fear stimulus (CS) (Milad and Quirk, 2012). Recent behavioral and pharmacological studies have reported participation of the BLA in fear extinction learning, including fear responses caused by the infusion of N-methyl-D-aspartic acid (NMDA) receptor (NMDAR) antagonists, mitogen-activated protein kinase (MAPk), or bupivacaine anesthetic (Herry et al, 2006; Kim et al, 2007; Sotres-Bayon et al, 2007). Consolidation involves activation of the phosphoinositide-3 kinase pathway in the BLA, synthesis of new proteins, and the expression of immediate early genes (Lin et al, 2003; Herry and Mons, 2004). These results have demonstrated that the BLA is involved in the acquisition and consolidation of extinction
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