The selective 5-HT1A receptor antagonist WAY-100635 inhibits neuronal activity of the ventromedial prefrontal cortex in a rodent model of Parkinson's disease.
OBJECTIVE
The ventral part of the medial prefrontal cortex (mPFC) plays an important role in initiation and control of voluntary movement, mood and cognition. However, after the degeneration of the nigrostriatal pathway, the neuronal activity of the ventral mPFC and the role of serotonin(1A) (5-hydroxytryptamine, 5-HT(1A)) receptors in the firing of the neurons are still unknown. The present study is to investigate the change of neuronal activity in the ventral mPFC and the effect of systemic administration of the selective 5-HT(1A) receptor antagonist WAY-100635 on the activity of the neurons in normal and 6-hydroxydopamine (6-OHDA)-lesioned rats.


METHODS
Single unit responses were recorded extracellularly with glass microelectrodes from ventral mPFC neurons in normal rats and 6-OHDA unilaterally lesioned rats in vivo.


RESULTS
6-OHDA lesion of the substantia nigra pars compacta (SNc) significantly increased the firing rate with no change in the firing pattern of neurons of the ventral mPFC in rats. Systemic administration of WAY-100635 (0.1 mg/kg, i.v.) did not change the mean firing rate and firing pattern of ventral mPFC neurons in normal rats. In contrast, WAY-100635 significantly decreased the mean firing rate of the neurons in rats with 6-OHDA lesion of the SNc.


CONCLUSIONS
These data suggest that the degeneration of the nigrostriatal pathway results in an increase of neuronal activity of ventral mPFC and dysfunction of 5-HT(1A) receptor.
Cao
Jian
J
Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
Liu
Jian
J
Zhang
Qiao-Jun
QJ
Wang
Tao
T
Wang
Shuang
S
Han
Ling-Na
LN
Li
Qiang
Q
D000200:Action Potentials; D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D017072:Neostriatum / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010300:Parkinson Disease / Q000503:physiopathology*; D010879:Piperazines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D013378:Substantia Nigra / Q000502:physiology
D010879:Piperazines; D011725:Pyridines; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide