Unilateral lesion of the nigrostriatal pathway decreases the response of interneurons in medial prefrontal cortex to 5-HT 2A/2C receptor stimulation in the rat.
The aim of the present study was to investigate changes in the firing rate and pattern of interneurons in the medial prefrontal cortex (mPFC), and effects of 5-HT(2A/2C) receptor agonist DOI and antagonist ritanserin, and the selective 5-HT(2C) receptor antagonist SB 242084 on the neuronal firing in rats with 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNc) by extracellular recording in vivo. The lesion of the SNc decreased the firing rate of the interneurons compared to sham-lesioned rats, and firing pattern of these interneurons changed toward a more burst-firing. Administration of DOI (20-320 microg/kg, i.v.) dose-dependently increased the firing rate of all interneurons examined in sham-lesioned and the 6-OHDA-lesioned rats. The excitation was significant at doses higher than 40 microg/kg and 320 microg/kg in sham-lesioned and the 6-OHDA-lesioned rats, respectively. This dose, which produced marked effect in the 6-OHDA-lesioned rats, was much higher than that of sham-lesioned rats. The local application of DOI (5 microg) in mPFC increased the firing rate of the interneurons in sham-lesioned rats, while having no effect on the firing rate in the 6-OHDA-lesioned rats. The excitatory effect of DOI in sham-lesioned and the 6-OHDA-lesioned rats was completely or partially reversed by ritanserin or SB 242084. The results of our study show that lesion of the SNc leads to a decrease in the firing rate of interneurons in mPFC and fire with a more burst pattern, and decreased response of the interneurons to DOI in rat.
Zhang
Qiao Jun
QJ
Department of Neurology, Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710004, China. zhangqj@mail.xjtu.edu.cn
Wang
Shuang
S
Liu
Jian
J
Ali
Umar
U
Gui
Zhen Hua
ZH
Wu
Zhong Heng
ZH
Hui
Yan Ping
YP
Wang
Yong
Y
Chen
Li
L
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D018663:Adrenergic Agents / Q000633:toxicity; D000631:Aminopyridines / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000293:injuries / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009434:Neural Pathways / Q000293:injuries / Q000502:physiology; D016627:Oxidopamine / Q000633:toxicity; D017397:Prefrontal Cortex / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D018490:Serotonin Agents / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects / Q000293:injuries / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D018663:Adrenergic Agents; D000631:Aminopyridines; D000662:Amphetamines; D018491:Dopamine Agonists; D007211:Indoles; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D018490:Serotonin Agents; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine