RESUMEN
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.
RESUMEN
The hippocampus, the primary brain structure related to learning and memory, receives sparse but comprehensive dopamine innervations and contains dopamine D1 and D2 receptors. Systematic hippocampal dopaminergic dysfunction can cause deficits in spatial working memory and impair consolidation of contextual fear memories. CA3 is involved in the rapid acquisition of new memories and has extensive nerve fibre connections with other brain structures such as CA1, the amygdala, and the medial prefrontal cortex (mPFC). A bidirectional fibrous connection between CA3 and the amygdala reflects the importance of CA3 in fear conditioning. The present study evaluated the effects of a 6-OHDA lesion in CA3 on the acquisition and expression of conditioned fear. The results showed CA3 involvement in the expression but not the acquisition of conditioned fear. Injection of SCH23390 and quinpirole into the bilateral CA3 attenuated a conditioned fear-related freezing response, whereas SKF38393 and sulpiride were not associated with this effect. The present study found that a 6-OHDA lesion in CA3 up-regulated the expression of GluR1 in BLA and down-regulated NR2B in CA1 and the basolateral amygdala (BLA). Our data suggest that dopamine depletion in hippocampal subdivision CA3 may not be necessary for the acquisition of conditioned fear, but the expression of conditioned fear is likely dependent on the integrity of mesohippocampal dopaminergic connections. It is probable that both D1 and D2 dopaminergic receptors modulate the expression of conditioned fear. Changes in the expression of NR2B and GluR1 indicate that CA3 may modulate the activities of other brain structures.