title: Activation and blockade of serotonin7 receptors in the prelimbic cortex regulate depressive-like behaviors in a 6-hydroxydopamine-induced Parkinson's disease rat model.
abstract: The role of serotonin7 (5-HT7) receptors in the regulation of depression is poorly understood, particularly in Parkinson's disease-associated depression. Here we examined whether 5-HT7 receptors in the prelimbic (PrL) sub-region of the ventral medial prefrontal cortex (mPFC) involve in the regulation of depressive-like behaviors in sham-operated rats and rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. The lesion induced depressive-like responses as measured by the sucrose preference and forced swim tests when compared to sham-operated rats. Intra-PrL injection of 5-HT7 receptor agonist AS19 (0.5, 1 and 2 μg/rat) increased sucrose consumption, and decreased immobility time in sham-operated and the lesioned rats, indicating the induction of antidepressant-like effects. Further, intra-PrL injection of 5-HT7 receptor antagonist SB269970 (1.5, 3 and 6 μg/rat) decreased sucrose consumption, and increased immobility time, indicating the induction of depressive-like responses. However, the doses producing these effects in the lesioned rats were higher than those in sham-operated rats. Neurochemical results showed that intra-PrL injection of AS19 (2 μg/rat) increased dopamine, 5-hydroxytryptamine (5-HT) and noradrenaline (NA) levels in the mPFC, habenula and ventral hippocampus (vHip) in sham-operated and the lesioned rats; whereas SB269970 (6 μg/rat) decreased 5-HT levels in the habenula and vHip, and the levels of NA in the mPFC, habenula and vHip in the two groups of rats. The results suggest that 5-HT7 receptors in the PrL play an important role in the regulation of these behaviors, which attribute to changes in monoamine levels in the limbic and limbic-related brain regions after activation and blockade of 5-HT7 receptors.
authors.affiliation: Department of Rehabilitation Medicine, The Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.
authors.forename: Q J
authors.initials: QJ
authors.lastname: Zhang
authors.affiliation: Department of Rehabilitation Medicine, The Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.
authors.forename: C X
authors.initials: CX
authors.lastname: Du
authors.affiliation: Department of Rehabilitation Medicine, The Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.
authors.forename: H H
authors.initials: HH
authors.lastname: Tan
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Rehabilitation Medicine, The Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.
authors.forename: L B
authors.initials: LB
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Medicine, The Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.
authors.forename: X L
authors.initials: XL
authors.lastname: Niu
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. Electronic address: liujian@mail.xjtu.edu.cn.
authors.forename: J
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism*; D019422:Dietary Sucrose; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology*; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D019422:Dietary Sucrose; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C104425:serotonin 7 receptor; D012701:Serotonin; D016627:Oxidopamine; D004298:Dopamine; D009638:Norepinephrine
keywords: 5-HT(7) receptors; Parkinson’s disease; depression; prelimbic cortex; rat