title: Dopamine D2/D3 but not dopamine D1 receptors are involved in the rapid antidepressant-like effects of ketamine in the forced swim test.
abstract: Major depressive disorder is one of the most prevalent and life-threatening forms of mental illnesses. The traditional antidepressants often take several weeks, even months, to obtain clinical effects. However, recent clinical studies have shown that ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, exerts rapid antidepressant effects within 2h and are long-lasting. The aim of the present study was to investigate whether dopaminergic system was involved in the rapid antidepressant effects of ketamine. The acute administration of ketamine (20 mg/kg) significantly reduced the immobility time in the forced swim test. MK-801 (0.1 mg/kg), the more selective NMDA antagonist, also exerted rapid antidepressant-like effects. In contrast, fluoxetine (10 mg/kg) did not significantly reduced the immobility time in the forced swim test after 30 min administration. Notably, pretreatment with haloperidol (0.15 mg/kg, a nonselective dopamine D2/D3 antagonist), but not SCH23390 (0.04 and 0.1 mg/kg, a selective dopamine D1 receptor antagonist), significantly prevented the effects of ketamine or MK-801. Moreover, the administration of sub-effective dose of ketamine (10 mg/kg) in combination with pramipexole (0.3 mg/kg, a dopamine D2/D3 receptor agonist) exerted antidepressant-like effects compared with each drug alone. In conclusion, our results indicated that the dopamine D2/D3 receptors, but not D1 receptors, are involved in the rapid antidepressant-like effects of ketamine.
authors.affiliation: Department of Physiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China; The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Physiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China; The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhuo R
authors.initials: ZR
authors.lastname: Zhu
authors.affiliation: Department of Physiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Bao C
authors.initials: BC
authors.lastname: Ou
authors.affiliation: Department of Physiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ya Q
authors.initials: YQ
authors.lastname: Wang
authors.affiliation: Department of Physiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhou B
authors.initials: ZB
authors.lastname: Tan
authors.affiliation: Department of Physiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Chang M
authors.initials: CM
authors.lastname: Deng
authors.affiliation: Department of Physiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yi Y
authors.initials: YY
authors.lastname: Gao
authors.affiliation: Department of Physiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China; The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Tang
authors.affiliation: Department of Physiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China; The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ji H
authors.initials: JH
authors.lastname: So
authors.affiliation: Department of Physiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China; The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yang L
authors.initials: YL
authors.lastname: Mu
authors.affiliation: Department of Physiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China; The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China; Tianjin Nankai Hospital, Tianjin, China. Electronic address: Lanqiuzhang@126.com.
authors.forename: Lan Q
authors.initials: LQ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D052160:Benzothiazoles / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D000077487:Pramipexole; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology*; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D001552:Benzazepines; D052160:Benzothiazoles; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D016194:Receptors, N-Methyl-D-Aspartate; C534628:SCH 23390; D005473:Fluoxetine; D007649:Ketamine; D016291:Dizocilpine Maleate; D000077487:Pramipexole; D006220:Haloperidol
keywords: Antidepressant; Depression; Dopamine receptor; Forced swim test; Ketamine