Background: Atomoxetine has been widely used for the treatment of attention-deficit/
hyperactivity disorder. ATX has additional abilities such as antagonistic effects on the N-methyl-Daspartate
receptors (NMDARs) and benefit effects in some animal models of neurological disorders.
However, there were few studies regarding protective effects and related mechanisms of ATX against
cerebral ischemic insults.
Objective: The objective of this study is to investigate neuroprotection of ATX pretreatment and its
mechanisms in the hippocampal cornu ammonis 1 (CA1) region following transient global cerebral
ischemia in gerbils.
Method: Gerbils were subjected to transient global cerebral ischemia induced by the occlusion of
common carotid arteries for 5 min. Thirty mg/kg of ATX was administrated intraperitoneally once
daily for 3 days before ischemic surgery. To examine neuroprotective effects of ATX, we carried
out neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B histofluorescence staining.
In addition, immunoreactivities of NMDAR1, NMDAR2A/B, B-cell lymphoma 2 (Bcl-2) and Bcl-2-
associated X protein (Bax) are closely related with neuroexcitotoxicity.
Results: ATX pretreatment reduced ischemia-induced hyperactivity and protected CA1 pyramidal
neurons from ischemia. Pretreatment with ATX significantly attenuated ischemia-induced increases
of NMDAR1 and NMDAR2A/B immunoreactivities in the CA1 pyramidal neurons at early time
following ischemia. In addition, significant ischemia-induced alterations of Bcl-2 and Bax
immunoreactivities were not observed in the ATX-treated group following ischemia.
Conclusion: These results show that pretreatment with ATX protected against ischemic neuronal via
inhibition of ischemia-induced excitotoxicity at early time following transient global cerebral ischemia.