Alterations in behavioral responses to dopamine agonists in olfactory bulbectomized mice: relationship to changes in the striatal dopaminergic system
Alterations in behavioral responses to dopamine agonists in olfactory bulbectomized mice: relationship to changes in the striatal dopaminergic system
复制标题
嗅球切除小鼠对多巴胺激动剂行为反应的改变：与纹状体多巴胺能系统变化的关系
DOI：
10.1007/s00213-016-4224-y
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发表时间：
2016
影响因子：
3.4
通讯作者：
Koichi Tan-No
中科院分区：
文献类型：
--
作者：
Kohei Takahashi;Osamu Nakagawasai;Wataru Nemoto;Takeharu Nakajima;Yuichiro Arai;Tadashi Hisamitsu;Koichi Tan-No
BackgroundOlfactory bulbectomy (OBX) in rodents is considered a putative animal model of depression. It has been reported that some abnormal behaviors observed in this animal model of depression involve dopaminergic neurons of the mesolimbic pathway. Therefore, we examined changes in the dopaminergic system in the caudate putamen (CPu), nucleus accumbens core (NAcC), and shell (NAcSh) of OBX mice and whether or not these alterations were reversed by chronic administration of imipramine.MethodsWe observed climbing behavior, which is a dopamine (DA) receptor-associated behavior, to demonstrate changes in the dopaminergic system of the mesolimbic pathway, when mice were administrated either the nonselective DA agonist apomorphine only or were pre-treated with the selective D1antagonist SCH23390, with the selective D2antagonist sulpiride, or with the D2/D3partial agonist aripiprazole (ARI). Moreover, we examined tyrosine hydroxylase (TH) and D1- and D2-like receptor levels in the CPu, NAcC, and NAcSh using immunohistochemistry and autoradiography.ResultsThe OBX group exhibited significantly enhanced apomorphine-induced climbing behavior, and this enhanced behavior was reversed by administration of sulpiride, ARI, and imipramine but not SCH23390. Moreover, we found a reduction in TH levels in the CPu, NAcC, and NAcSh of OBX mice and an increase in D2receptor densities in the NAcC of OBX mice. The increased D2receptor density observed in OBX mice was reversed by imipramine administration.ConclusionsThese findings reveal that OBX mice display enhanced DA receptor responsiveness, which may relate to some of the behavioral abnormalities reported in this animal model.
