The effects of intra-hippocampal microinfusion of d-cycloserine on fear extinction, and the expression of NMDA receptor subunit NR2B and neurogenesis in the hippocampus in rats

Abstract

Pharmacological and behavior interventions for inhibiting fear and anxiety are important in the treatment of different types of anxiety disorder. Fear extinction, as a novel form of associative learning, is the most extensively studied models to understand the neural mechanisms of fear-related and anxiety disorders. One of the possible mechanisms of neural plasticity in extinction learning may depend on activation of NMDA receptors in the amygdale; however, the role played by the hippocampus in extinction remains largely unclear. In the present study, using a fear conditioning paradigm, we repeatedly microinfused D-cycloserine, a partial agonist of NMDA receptor, into the hippocampus and investigated the effects of repeated infusions of DCS on extinction behavior and protein levels of NMDA receptor subunit NR2B. We also examined the effects of DCS on neurogenesis in adult rat hippocampus. Our results showed that the administration of DCS facilitated the acquisition and retrieval of extinction memory, and enhanced the expression of NR2B protein in the dentate gyrus, CA1 and CA3 of the hippocampus. We also found that repeated microinfusions of DCS increased proliferation of newly born cells in the hippocampus. These findings suggest that neural plasticity mediated by NMDA receptors in the hippocampus is involved in the enhancement of acquisition and retrieval of extinction memory.