Repeated stress prevents cocaine-induced activation of BDNF signaling in rat prefrontal cortex |
| |
| Affiliation: | 1. Department of Immunology, Weizmann Institute of Science, Rehovot 761001, Israel;2. Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 761001, Israel;1. Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, United States;2. Carolina Medical Center, Multiple Sclerosis Center, Charlotte, North Carolina, 28207, United States;3. Rutgers University, Department of Statistics and Biostatistics, Piscataway, NJ 08854, United States;1. Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran;2. Department of Research and Development, SodourAhrarShargh Company, Tehran, Iran;3. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran;1. Department of Pharmacological and Biomolecular Sciences, University of Milan, I-20133 Milan, Italy;2. Center of Excellence on Neurodegenerative Diseases, University of Milan, I-20133 Milan, Italy;1. Istituto Superiore di Sanità, Department of Therapeutic Research and Medicines Evaluation, Viale Regina Elena 299, 00161 Rome, Italy;2. Department of Medical Sciences, Pharmacology Section, University of Ferrara, via Fossato di Mortara 17/19, 44121 Ferrara, Italy;3. Department of Life Sciences and Biotechnology, University of Ferrara, Via Fossato di Mortara 17, 44121 Ferrara, Italy |
| |
| Abstract: | In this report we provide evidence that repeated stress prevents cocaine-induced activation of BDNF expression and signaling in rat prefrontal cortex. A single injection of cocaine up-regulates BDNF expression in sham (i.e. unstressed) rats but not in repeatedly stressed rats. Similarly, the expression as well as trafficking of the high affinity BDNF receptor trkB promoted by the psychostimulant is impaired in chronically-stressed rats challenged with cocaine.Moreover, among the different intracellular signaling pathways that can be activated by the neurotrophin, i.e. ERK1/2-, Akt- and PLCγ-pathway, we found that cocaine is able to selectively activate the ERK1/2 pathway in sham animals, but not in rats exposed to repeated stress. Notably, such changes take place in chronically-stressed animals although they still retain the ability to increase neuronal activity as measured by the enhancement of Arc gene expression.In summary, we have demonstrated that stress globally interferes with BDNF-mediated signaling responses to cocaine challenge, providing key insights into the molecular basis of stress-cocaine interaction and indicating the critical role of the prefrontal cortex in mediating such interaction. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
