title: Activation of prelimbic 5-HT1A receptors produces antidepressant-like effects in a unilateral rat model of Parkinson's disease.
abstract: Depression is a common symptom in Parkinson's disease (PD), but its pathophysiology remains unclear. Several lines of studies have revealed that the prelimbic (PrL) sub-region of the ventral medial prefrontal cortex and 5-HT1A receptors are involved in the regulation of depression. In this study, we examined whether complete unilateral lesions of the medial forebrain bundle (MFB) using 6-hydroxydopamine in rats are able to induce depressive-like behaviors, the role of PrL 5-HT1A receptors in the regulation of these behaviors, and co-localization of 5-HT1A receptor and neuronal glutamate transporter EAAC1-immunoreactive (EAAC1-ir) neurons in the PrL. The MFB lesions induced depressive-like responses as measured by the sucrose preference and forced swim tests when compared to sham-operated rats. The intra-PrL injection of 5HT1A receptor agonist 8-OH-DPAT (50, 100, and 500ng/rat) increased sucrose consumption, and decreased immobility time in both sham-operated and the lesioned rats, indicating the induction of antidepressant effects. Furthermore, the intra-PrL injection of 5HT1A receptor antagonist WAY-100635 (60, 120, and 240ng/rat) showed a decrease in sucrose consumption, and an increase in immobility time, indicating the induction of depressive-like responses. However, the effective doses in the lesioned rats were higher than those in sham-operated rats, which attribute to down-regulation of 5-HT1A receptor expression on EAAC1-ir neurons in the PrL of the lesioned rats. These findings suggest that unilateral lesions of the MFB in rats may induce depressive-like behaviors, and 5-HT1A receptors of the PrL play an important role in the regulation of these behaviors.
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Y P
authors.initials: YP
authors.lastname: Hui
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 Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Rehabilitation Medicine, The Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.
authors.forename: H F
authors.initials: HF
authors.lastname: Qiao
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: yongwang@mail.xjtu.edu.cn.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: liujian@mail.xjtu.edu.cn.
authors.forename: J
authors.initials: J
authors.lastname: Liu
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy / Q000503:physiopathology*; D019422:Dietary Sucrose / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism; D005518:Food Preferences / Q000187:drug effects / Q000502:physiology; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000503:physiopathology* / Q000523:psychology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D019422:Dietary Sucrose; D050580:Excitatory Amino Acid Transporter 3; D010879:Piperazines; D011725:Pyridines; D058829:Serotonin 5-HT1 Receptor Antagonists; D017366:Serotonin Receptor Agonists; C493398:Slc1a1 protein, rat; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D016627:Oxidopamine
keywords: 5-HT(1A) receptors; Parkinson’s disease; depression; prelimbic medial prefrontal cortex; rat