title: Alterations in behavioral responses to dopamine agonists in olfactory bulbectomized mice: relationship to changes in the striatal dopaminergic system.
abstract: BACKGROUND
  Olfactory 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.
  
  
  METHODS
  We 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 D1 antagonist SCH23390, with the selective D2 antagonist sulpiride, or with the D2/D3 partial 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.
  
  
  RESULTS
  The 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 D2 receptor densities in the NAcC of OBX mice. The increased D2 receptor density observed in OBX mice was reversed by imipramine administration.
  
  
  CONCLUSIONS
  These findings reveal that OBX mice display enhanced DA receptor responsiveness, which may relate to some of the behavioral abnormalities reported in this animal model.
authors: Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan.
authors: Kohei
authors: K
authors: Takahashi
authors: Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan. osamun@tohoku-pharm.ac.jp.
authors: Osamu
authors: O
authors: Nakagawasai
authors: Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan.
authors: Wataru
authors: W
authors: Nemoto
authors: Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan.
authors: Takeharu
authors: T
authors: Nakajima
authors: Department of Health Science, Ariake University of Medical and Health Science, 2-9-1 Ariake, Koto-Ku, Tokyo, 135-0063, Japan.
authors: Yuichiro
authors: Y
authors: Arai
authors: Department of Physiology, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8666, Japan.
authors: Tadashi
authors: T
authors: Hisamitsu
authors: Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan.
authors: Koichi
authors: K
authors: Tan-No
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003863:Depression / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D009830:Olfactory Bulb / Q000187:drug effects / Q000378:metabolism / Q000601:surgery*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012903:Smell / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; D007099:Imipramine; D004298:Dopamine
keywords: Climbing behavior; Depression; Dopamine; Olfactory bulbectomy; Tyrosine hydroxylase