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Neuropharmacology. 2015 Jun;93:68-79. doi: 10.1016/j.neuropharm.2015.01.024. Epub 2015 Feb 7.

Activation of serotonin(2C) receptors in the lateral habenular nucleus increases the expression of depression-related behaviors in the hemiparkinsonian rat.

Author information

1
Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
2
Department of Rehabilitation Medicine, the Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.
3
Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: liujian@mail.xjtu.edu.cn.

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.

KEYWORDS:

5-HT(2C) receptors; Depression; Glutamate neurons; Lateral habenular nucleus; Parkinson's disease

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