title: Activation of serotonin(2C) receptors in the lateral habenular nucleus increases the expression of depression-related behaviors in the hemiparkinsonian rat.
abstract: The roles of lateral habenular nucleus (LHb) glutamate neurons and serotonin2C (5-HT2C) receptors in depression are poorly understood, particularly in Parkinson's disease-associated depression. Here we assessed the importance of LHb glutamate neurons and 5-HT2C receptors for depressive-like behaviors in sham-operated rats and rats with unilateral 6-hydroxydopamine lesions of the substantia nigra. The lesion induced depressive-like responses compared to sham-operated rats. Intra-LHb injection of potent, selective 5-HT2C receptor agonist Ro60-0175 decreased sucrose consumption and increased immobility time in sham-operated rats, indicating the induction of depressive-like responses, and intra-LHb injection of Ro60-0175 further increased the expression of depressive-like behaviors in the lesioned rats. Activation of LHb 5-HT2C receptors by the local administration of Ro60-0175 increased the firing rate of EAAC1 (a neuronal glutamate transporter)-positive neurons and percentage of the neurons with burst-firing pattern in the two groups of rats. Compared to sham-operated rats, the duration of Ro60-0175 action on the firing rate of EAAC1-positive neurons was markedly prolonged in the lesioned rats. Intra-LHb injection of Ro60-0175 decreased dopamine, 5-HT and noradrenaline levels in the medial prefrontal cortex, habenula, hippocampus and amygdala in sham-operated and the lesioned rats. The lesion did not change the percentage of EAAC1/5-HT2C receptor co-expressing neurons in the LHb. These findings indicate that activation of 5-HT2C receptors in the LHb increases firing activity of LHb glutamate neurons and then decreases monoamine levels in several brain regions, which increase the expression of depressive-like behaviors. Further, our results also suggest that the lesion leads to hyperfunctionality of 5-HT2C receptors on glutamate neurons of the LHb.
authors: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors: Ling-Na
authors: LN
authors: Han
authors: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors: Li
authors: L
authors: Zhang
authors: Department of Rehabilitation Medicine, the Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.
authors: Li-Bo
authors: LB
authors: Li
authors: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors: Yi-Na
authors: YN
authors: Sun
authors: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors: Yong
authors: Y
authors: Wang
authors: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors: Li
authors: L
authors: Chen
authors: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors: Yuan
authors: Y
authors: Guo
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 Rehabilitation Medicine, the Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.
authors: Qiao-Jun
authors: QJ
authors: Zhang
authors: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: liujian@mail.xjtu.edu.cn.
authors: Jian
authors: J
authors: Liu
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003863:Depression / Q000209:etiology* / Q000473:pathology*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D005518:Food Preferences / Q000187:drug effects; D007839:Functional Laterality / Q000187:drug effects; D019262:Habenula / Q000378:metabolism* / Q000473:pathology; D008297:Male; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000150:complications*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects; D013395:Sucrose / Q000008:administration & dosage; D013550:Swimming / Q000523:psychology
chemical_list: D018663:Adrenergic Agents; D018491:Dopamine Agonists; D044405:Receptor, Serotonin, 5-HT2C; D018490:Serotonin Agents; D013395:Sucrose; D016627:Oxidopamine; D001058:Apomorphine
keywords: 5-HT(2C) receptors; Depression; Glutamate neurons; Lateral habenular nucleus; Parkinson's disease