1. 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.
- Author
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Wang S, Zhang QJ, Liu J, Ali U, Wu ZH, Chen L, Gui ZH, Wang Y, and Hui YP
- Subjects
- Action Potentials drug effects, Amphetamines pharmacology, Animals, Disease Models, Animal, Dose-Response Relationship, Drug, GABA Antagonists pharmacology, Interneurons drug effects, Interneurons metabolism, Male, Oxidopamine, Parkinson Disease physiopathology, Prefrontal Cortex cytology, Prefrontal Cortex drug effects, Pyramidal Cells cytology, Pyramidal Cells drug effects, Rats, Rats, Sprague-Dawley, Receptor, Serotonin, 5-HT2A drug effects, Ritanserin pharmacology, Serotonin metabolism, Serotonin Antagonists pharmacology, Serotonin Receptor Agonists pharmacology, Sympatholytics, Synaptic Transmission drug effects, Synaptic Transmission physiology, gamma-Aminobutyric Acid metabolism, Action Potentials physiology, Parkinson Disease metabolism, Prefrontal Cortex metabolism, Pyramidal Cells metabolism, Receptor, Serotonin, 5-HT2A metabolism, Serotonin Agents pharmacology
- Abstract
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.
- Published
- 2009
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