We previously reported that the lipopolysaccharide (LPS)-induced depressive-like behavior is associated with α₁-adrenoceptor dependent membrane AMPA receptor GluR1 subunit downregulation in the reward system. However, induction of membrane GluR1 downregulation in specifically reward system caused anhedonia, but not despair behavior. Recently, we found that α₁-adrenoceptor in the bed nucleus of stria terminalis (BNST) regulate the learned despair in mice. Since the α₁-adrenoceptor in BNST dependent long-term synaptic depression is induced via increase in the Ca²⁺ impermeable AMPA receptor by RNA editing of GluR2, we investigated whether Ca²⁺ impermeable AMPA receptor in BNST contribute to the LPS-induced despair behavior. To mimic the GluR2 RNA editing, we bilaterally injected 1-Naphthylacetyl spermine (Naspm), a Ca²⁺ permeable AMPA receptor blocker, into BNST in awake mice 24 h after LPS injection. Naspm did not affect the body weight, locomotor activity and sucrose preference in LPS-challenged mice. However, immobility time during the tail suspension was significantly increased by Naspm. We suggest that the GluR2 RNA-editing in BNST contribute to the LPS-induced behavioral despair in mice.