title: Serotonin₆ receptors in the dorsal hippocampus regulate depressive-like behaviors in unilateral 6-hydroxydopamine-lesioned Parkinson's rats.
abstract: Preclinical studies indicate both activation and blockade of serotonin6 (5-HT6) receptors may produce antidepressant-like effects. Depression is a common symptom in Parkinson's disease (PD); however, its pathophysiology is unclear. Here we examined whether 5-HT6 receptors in the dorsal hippocampus (DH) involve in the regulation of PD-associated depression. Unilateral 6-hydroxydopamine lesions of the medial forebrain bundle in rats induced depressive-like responses as measured by the sucrose preference and forced swim tests when compared to sham-operated rats. In sham-operated rats, intra-DH injection of 5HT6 receptor agonist WAY208466 or antagonist SB258585 increased sucrose consumption and decreased immobility time, indicating the induction of antidepressant effects. In the lesioned rats, WAY208466 also produced antidepressant effects, whereas SB258585 decreased sucrose consumption and increased immobility time, indicating the induction of depressive-like behaviors. Neurochemical results showed that WAY208466 did not change dopamine (DA) levels in the medial prefrontal cortex (mPFC), DH and habenula, and noradrenaline (NA) levels in the DH and habenula in sham-operated rats, and SB258585 increased DA and NA levels in these structures. Further, WAY208466 increased DA levels in the mPFC, DH and habenula, and NA level in the habenula in the lesioned rats, and SB258585 decreased DA levels in the mPFC and habenula. Additionally, the lesion did not change the density of neuronal glutamate transporter EAAC1/5-HT6 receptor co-expressing neurons in the DH. Compared to sham-operated rats, these findings suggest that the effects of 5-HT6 receptors in PD-associated depression may be mediated through different neurochemical mechanisms, and the DH is an important site involved in these effects.
authors: Department of Clinical Medicine, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors: Kun-Cheng
authors: KC
authors: Liu
authors: Department of Clinical Medicine, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors: Jun-Yi
authors: JY
authors: Li
authors: Department of Rehabilitation Medicine, the Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.
authors: Hui-Hui
authors: HH
authors: Tan
authors: Department of Rehabilitation Medicine, the Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.
authors: Cheng-Xue
authors: CX
authors: Du
authors: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors: Wen
authors: W
authors: Xie
authors: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors: Yu-Ming
authors: YM
authors: Zhang
authors: Department of Clinical Medicine, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors: Wei-Lin
authors: WL
authors: Ma
authors: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: zhangli1998@mail.xjtu.edu.cn.
authors: Li
authors: L
authors: Zhang
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D003866:Depressive Disorder / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism; D019262:Habenula / Q000187:drug effects / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008474:Medial Forebrain Bundle; D008744:Methylamines / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000503:physiopathology* / Q000523:psychology; D010879:Piperazines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology; D011725:Pyridines / Q000494:pharmacology; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D050580:Excitatory Amino Acid Transporter 3; D008744:Methylamines; C558330:N-(2-(3-(3-fluorophenylsulfonyl)-1H-pyrrolo(2,3-b)pyridin-1-yl)ethyl)-N,N-dimethylamine; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; C418570:SB 258585; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C493398:Slc1a1 protein, rat; D013449:Sulfonamides; C097216:serotonin 6 receptor; D016627:Oxidopamine; D004298:Dopamine; D009638:Norepinephrine
keywords: 5-HT(6) receptors; Depression; Dopamine; Dorsal hippocampus; Noradrenaline; Parkinson's disease; Rat; Serotonin