Norepinephrine in the dentate gyrus is involved in spatial learning and memory alteration induced by chronic...

The role of norepinephrine of the hippocampal dentate gyrus in spatial learning and memory alteration induced by chronic restraint stress (CRS, 3 h/day, 6 weeks) was investigated in aged rats. Spatial learning and memory were assessed by the Morris water maze (MWM), and the extracellular concentration of norepinephrine and amplitude of field excitatory postsynaptic potential (fEPSP) were measured in the dentate gyrus during MWM test in freely-moving rats. Next, the involvement of β-adrenoceptors in spatial learning and memory of CRS rats was examined by microinjection of its antagonist (propranolol) into the dentate gyrus. In addition, we observed the expression of brain-derived neurotrophic factor (BDNF) protein and activation of cAMP-response element binding protein (CREB) in the dentate gyrus. Compared with the control group, the basal level of norepinephrine, BDNF expression and CREB activation in the dentate gyrus were increased, and the spatial learning and memory abilities were enhanced in CRS rats. In the control group, the norepinephrine concentration and fEPSP amplitude in the dentate gyrus were increased on the second to fourth days of MWM test, and these responses were significantly enhanced in CRS rats. Furthermore, in CRS rats, propranolol significantly decreased the spatial learning and memory abilities, and attenuated the fEPSP response during MWM test, and the BDNF expression and CREB activation in the dentate gyrus. Our results suggest that norepinephrine activation of β-adrenoceptors in the hippocampal dentate gyrus is involved in spatial learning and memory enhancement induced by CRS in aged rats, in part via modulations of synaptic efficiency and CREB-BDNF signaling pathway.