In vivo effects of activation and blockade of 5-HT(2A/2C) receptors in the firing activity of pyramidal neurons of medial prefrontal cortex in a rodent model of Parkinson's disease.
In the present study, we examined changes in the firing rate and firing pattern of pyramidal neurons in medial prefrontal cortex (mPFC), and the effects of 5-HT(2A/2C) receptor agonist DOI and antagonist ritanserin on the neuronal firing in rats with 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta by using extracellular recording. The unilateral lesion of the nigrostriatal pathway significantly increased the mean firing rate of pyramidal neurons compared to sham-operated rats, and the firing pattern of these neurons also changed significantly towards a more bursty one. Systemic administration of DOI (20-320 microg/kg, i.v.) increased the mean firing rate of pyramidal neurons in sham-operated and the lesioned rats. The excitation was significant only at doses higher than 160 microg/kg and 320 microg/kg in sham-operated and the lesioned rats, respectively. In addition, the local application of DOI, 5 microg, in mPFC inhibited the firing rate of pyramidal neurons in sham-operated rats, while having no effect on firing rate in the lesioned rats. After treatment with GABAA receptor antagonist picrotoxinin, the local application of DOI, at the same dose, increased the mean firing rate of the neurons in sham-operated rats; however, DOI did not alter the firing activity of the neurons in the lesioned rats. These results indicate that the lesion of the nigrostriatal pathway leads to hyperactivity of pyramidal neurons in mPFC, and the decreased response of pyramidal neurons to DOI, suggesting dysfunction of 5-HT2A and 5-HT2C receptors on pyramidal neurons and GABAergic interneurons in the 6-OHDA-lesioned rats.
Wang
Shuang
S
Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
Zhang
Qiao Jun
QJ
Liu
Jian
J
Ali
Umar
U
Wu
Zhong Heng
ZH
Chen
Li
L
Gui
Zhen Hua
ZH
Wang
Yong
Y
Hui
Yan Ping
YP
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016627:Oxidopamine; D010300:Parkinson Disease / Q000378:metabolism* / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000378:metabolism*; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013565:Sympatholytics; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000662:Amphetamines; D018756:GABA Antagonists; D044402:Receptor, Serotonin, 5-HT2A; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013565:Sympatholytics; D016713:Ritanserin; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D016627:Oxidopamine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine