Uncontrollable, But Not Controllable, Stress Desensitizes 5-HT1AReceptors in the Dorsal Raphe Nucleus
| Autor: | Linda R. Watkins, Robert R. Rozeske, Steven F. Maier, Matthew G. Frank, Andrew K. Evans, Christopher A. Lowry |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Agonist Serotonin medicine.medical_specialty medicine.drug_class medicine.medical_treatment Action Potentials Serotonergic Article Rats Sprague-Dawley chemistry.chemical_compound Dorsal raphe nucleus Internal medicine medicine Animals Desensitization (medicine) Electroshock Dose-Response Relationship Drug General Neuroscience Rats Endocrinology nervous system Muscimol chemistry Receptor Serotonin 5-HT1A Autoreceptor Raphe Nuclei Raphe nuclei Psychology Stress Psychological |
| Zdroj: | The Journal of Neuroscience. 31:14107-14115 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | Uncontrollable stressors produce behavioral changes that do not occur if the organism can exercise behavioral control over the stressor. Previous studies suggest that the behavioral consequences of uncontrollable stress depend on hypersensitivity of serotonergic neurons in the dorsal raphe nucleus (DRN), but the mechanisms involved have not been determined. We usedex vivosingle-unit recording in rats to test the hypothesis that the effects of uncontrollable stress are produced by desensitization of DRN 5-HT1Aautoreceptors. These studies revealed that uncontrollable, but not controllable, tail shock impaired 5-HT1Areceptor-mediated inhibition of DRN neuronal firing. Moreover, this effect was observed only at time points when the behavioral effects of uncontrollable stress are present. Furthermore, temporary inactivation of the medial prefrontal cortex with the GABAAreceptor agonist muscimol, which eliminates the protective effects of control on behavior, led even controllable stress to now produce functional desensitization of DRN 5-HT1Areceptors. Additionally, behavioral immunization, an experience with controllable stress before uncontrollable stress that prevents the behavioral outcomes of uncontrollable stress, also blocked functional desensitization of DRN 5-HT1Areceptors by uncontrollable stress. Last, Western blot analysis revealed that uncontrollable stress leads to desensitization rather than downregulation of DRN 5-HT1Areceptors. Thus, treatments that prevent controllable stress from being protective led to desensitization of 5-HT1Areceptors, whereas treatments that block the behavioral effects of uncontrollable stress also blocked 5-HT1Areceptor desensitization. These data suggest that uncontrollable stressors produce a desensitization of DRN 5-HT1Aautoreceptors and that this desensitization is responsible for the behavioral consequences of uncontrollable stress. |
| Databáze: | OpenAIRE |
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