Effect Of Dopamine Receptor Antagonists To Anxiety-like Behavior And A Tyrosine Hydroxylase Expression In The Substantia Nigra After Hypoxic Ischemic Brain Damage In Vivo

Objectives:Using neonatal Sprague-Dawley(SD) rat hypoxic ischemic brain damage (HIBD) model to observe the long term change of anxiety-like behavior and tyrosine hydroxylase(TH) expression in the substantia nigra(SN) area after HIBD, and to explore the influence of dopamine receptor(DAR) antagonist to the long term anxiety-like behavior.Methods:Neonatal SD rats were randomly divided into normal control, sham operated, HIBD and HIBD+DAR antagonist groups on postnatal day (P7). DAR antagonist was intraperitoneally given before HIBD. Anxiety-like behavior was measured by elevated plus maze (EPM) at P14, P21and P28. TH expression in the SN area was detected by immunohistochemistry at P14, P21and P28.Results:1. Anxiety-like behavior:(1) The time spent in open arms, the percentage of open arms entry and the total arms entry were no significant difference in four groups at P14(P<0.05).(2) At P21the time spent in open arms in HIBD group was longer than normal control group (Z=-2.12, P=0.03), sham operated group (Z=-2.42, P=0.02) and HIBD+DAR antagonist group (Z=-2.04, P=0.04). The percentage of open arms entry in HIBD group was higher than normal control group (Z=-2.03, P=0.04), sham operated group (Z=-2.71, P=0.00) and HIBD+DAR antagonist group (Z=-2.79, P=0.00).(3) At P21the time spent in open arms in HIBD group was longer than normal control group (Z=-3.70, P=0.00), sham operated group (Z=-3.33, P=0.00) and HIBD+DAR antagonist group (Z=-2.04, P=0.04). The percentage of open arms entry in HIBD group was higher than normal control group (Z=-3.36, P=0.00), sham operated group (Z=-6.61, P=0.00) and HIBD+DAR antagonist group (Z=-2.55,P=0.01).2. TH imminohistochemistry expression:The expression of TH in HIBD group was less than in HIBD+DAR antagonist group (P<0.05), the expression of TH in HIBD+DAR antagonist group was less than normal control and sham operated groups (P<0.05).Conclusions:1. The change of long term anxiety-like behavior in SD rats after HIBD is related to the dopaminergic neuronal damage and the decreased expression of TH in SN area.2. DAR antagonist can regain the long term anxiety-like behavior to normal level after HIBD, confirm that the change of DA level is relate to the long term anxiety-like behavior in SD rats after HIBD. Eleven figures, three tables and fifty-nine references in this article.