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| Author(s): |
Daniele Cristina de Aguiar
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Ribeirão Preto. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) |
| Defense date: | 2008-10-03 |
| Examining board members: |
Francisco Silveira Guimarães;
Newton Sabino Canteras;
Antonio de Pádua Carobrez;
Leda Menescal de Oliveira
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| Advisor: | Francisco Silveira Guimarães |
| Abstract | |
Nitric oxide (NO) is synthesized by NO synthase (NOSn) and plays a role in defensive reactions, probably increasing anxiety responses. NOSn containing neurons are localized in different regions of the central nervous system related to defensive behavior such as the dorsolateral periaqueductal gray (dlPAG) and the dorsal premammillary nucleus (PMd). Glutamate antagonists and NOS inhibitors injected into the dlPAG induce anxiolytic responses. Exposure to an innate fear stimulus (live cat) induces defensive reactions and activation of NO producing neurons in this region. The dlPAG receives inputs from the PMd, which appears to be related to defensive reactions. Bilateral ibotenic acid lesions of the PMd virtually eliminate the expression of defensive responses. Little is known about the neurotransmitters responsible for the behavioral responses mediated by the PMd, which also expresses ionotropic glutamate receptors. The aim of this study was to verify the involvement of NO and glutamate neurotransmission in defensive reactions modulated by dlPAG and PMd. First, we tested the hypothesis that the injection of NOS inhibitors, 7-NI or NP, directly into the dlPAG would attenuate defensive reactions induced by exposure to a live predator. We also tested the hypothesis that the injection of AP-7 (glutamate NMDA-receptor antagonist) or NP into the dlPAG would attenuate the behavioral responses and cellular activation following exposure to a live predator. c-Fos expression was employed as a marker of neuronal functional activation whereas NOSn immunohistochemistry was used to detect the presence of NOS neurons. Finally, we tested the hypothesis that the injection of AP-7 or NP into the PMd would attenuate the defensive reactions induced by a live cat. Cat exposure induced fear responses which were attenuated by NOS inhibitors or AP-7 when injected into the dlPAG. The cat exposure increased cFos positive cells in both sides of dlPAG, PMd and in the periventricular nucleus (PVN). lt also increased the percentage of double stained cells (% DS) in the dlPAG and in the PMd. Pretreatment with AP-7 or NP in the dlPAG decreased the cellular effects induced by predator exposure in the dlPAG and PVN, while increased the number of cFos positive cells and % DS in the PMd. Moreover, pretreatment with AP-7 or NP into the PMd also attenuated the behavioral responses induced by live cat. These results suggest that inhibition of glutamate or nitric oxide neurotransmission in the dlPAG and the PMd can attenuate behavioral responses to threatening stimuli. Additionally, AP-7 or NP pretreatment in the dlPAG was able to reduce the cellular effects induced by predator exposure in this structure. These treatments, however, did no change and even increased the cellular effects in other regions related to defensive reactions such as the PMd. (AU) | |