Journal
EXPERIMENTAL NEUROLOGY
Volume 219, Issue 1, Pages 239-248Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2009.05.029
Keywords
5-Hydroxytryptamine; 5-HT2A receptors; 5-HT2C receptors; Medial prefrontal cortex; Pyramidal neurons; GABAergic interneurons; 6-Hydroxydopamine; Parkinson's disease; Electrophysiology
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Funding
- Natural Science Foundation [SJ08C210]
- Science and Technological Project of Shaanxi Province, China [2008K15-01(9)]
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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-HT2A/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 mu g/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 mu g/kg and 320 mu g/kg in sham-operated and the lesioned rats, respectively. In addition, the local application of DOI, 5 mu g, 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 GABA(A) 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. (C) 2009 Elsevier Inc. All rights reserved.
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