title: Involvement of lateral habenula α1 subunit-containing GABAAreceptor-mediated inhibitory transmission in the regulation of depression-related behaviors in experimental Parkinson's disease.
abstract: The lateral habenula (LHb) plays an important role in the regulation of depression. At present, it is not clear whether GABAAreceptor-mediated inhibitory transmission in the LHb is involved in Parkinson's disease (PD)-associated depression. In this study, unilateral 6-hydroxydopamine lesions of the substantia nigra in rats induced depressive-like behaviors and led to hyperactivity of LHb neurons compared to sham-operated rats, which attribute to depletion of dopamine, and decreased synthesis and release of GABA and increased release of glutamate in the LHb. Intra-LHb injection of GABAAreceptor agonist muscimol produced antidepressant-like effects, while the injection of GABAAreceptor antagonist picrotoxin induced or increased the expression of depressive-like behaviors in sham-operated and the lesioned rats. However, the doses producing these behavioral effects in the lesioned rats were lower than those in sham-operated rats. Intra-LHb injection of muscimol decreased the firing rate of LHb neurons and increased the medial prefrontal cortex serotonin (5-HT) release; conversely, picrotoxin increased the firing rate of the neurons and decreased 5-HT release in two groups of rats. Compared to sham-operated rats, the duration of muscimol and picrotoxin action on the firing rate of the neurons and 5-HT release was prolonged in the lesioned rats. These changes in the lesioned rats were associated with up-regulation of the expression of α1 subunit-containing GABAAreceptors and reduction of GABA release in the LHb. Collectively, our findings suggest that degeneration of the nigrostriatal pathway impairs GABAAreceptor-mediated inhibitory transmission in the LHb, and the transmission is important for regulating PD-associated depression.
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: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China, Xi'an 710061, China.
authors.forename: Li
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: Qiao-Jun
authors.initials: QJ
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China, Xi'an 710061, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
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: Cheng-Xue
authors.initials: CX
authors.lastname: Du
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: Yi-Na
authors.initials: YN
authors.lastname: Sun
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: Jin
authors.initials: J
authors.lastname: Zhang
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: Shu-Xuan
authors.initials: SX
authors.lastname: Lv
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China, Xi'an 710061, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China, Xi'an 710061, China. Electronic address: liujian@mail.xjtu.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003863:Depression / Q000378:metabolism* / Q000473:pathology; D018491:Dopamine Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D019262:Habenula / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000473:pathology / Q000523:psychology*; D010852:Picrotoxin / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism
chemical_list: D001058:Apomorphine; D018491:Dopamine Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D009118:Muscimol; D016627:Oxidopamine; D010852:Picrotoxin; D011963:Receptors, GABA-A; D012701:Serotonin; C546242:Gabra1 protein, rat
keywords: Depression; GABAergic transmission; Glutamate; Lateral habenula; Monoamines; Parkinson's disease