| Grant number: | 11/00041-3 |
| Support Opportunities: | Research Projects - Thematic Grants |
| Start date: | August 01, 2011 |
| End date: | July 31, 2015 |
| Field of knowledge: | Biological Sciences - Pharmacology - Neuropsychopharmacology |
| Principal Investigator: | Marcus Lira Brandão |
| Grantee: | Marcus Lira Brandão |
| Host Institution: | Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil |
| City of the host institution: | Ribeirão Preto |
| Associated scholarship(s): | 14/02000-0 - Characterization of the dopamine role in the mediation of distinct kinds of fear, BP.PD |
Abstract
The neural substrates responsible for fear and anxiety translate information of aversive nature in behavioral and emotional adaptive output reactions functioning as a sensorimotor gating for the threatening conditions which we face with in our daily life. Evidence from several sources indicates that these sensorimotor gatings are activated by aversive information associated with immediate actions such as certain sounds emmited by preys, predators or conspecifics. Malfunctioning sensorimotor gatings may underlie faulty responses to the dangerous environment and be the cause of maldaptive reasponses associated with anxiety states. The medial hypothalamus, amygdala and dorsal periaqueductal gray (dPAG) have been traditionally grouped together as a "encephalic aversion system" (EAS). More recently, a continuos strip of midbrain structures composed of superior and inferior colliculi have also been proposed as part of this "system". The stimulation of some structures of the EAS may represent an animal model for certain types of anxiety since the gradual increase in the intensity of its electrical stimulation produce initially alertness, then freezing, and finally escape reactions. Recent evidence obtained during the development of the last thematic project of this laboratory funded by FAPESP has also pointed out the dPAG post-stimulation freezing, which appears to be an index of the state of agony we feel after having faced with intense danger or panic attack. It has been proposed that GABAergic mechanisms are involved in the gating of distinct sensory information of aversive nature depending on the midbrain structure which is activated; visual in the superior colliculus, tactile-nociceptive in the dPAG or auditory in the inferior colliculus. Besides GABA, also 5-HT, opioids, and excitatory amino acids have all been implicated in the regulation of anxiety-related behaviors induced by stimulation of midbrain tectum. However, the dopaminergic and neurocininergic mediation of these emotional reactions have not been thoroughly investigated. For example, based on pharmacological evidence it has been shown that dopaminergic mechanisms seem to be involved in the expression of adaptive responses to threatening situations in the inferior colliculus, but not in the dPAG. In this respect, the prefrontal cortex and the core and shell subregions of the nucleus accumbens (NAC) may also contribute to the organization of defensive reactions to threatening and dangerous situations.It is clear nowadays that the understanding of the neurochemical, anatomical and genetic substrates of fear and anxiety must take into account the chemistry of the midbrain tectum "defense-system" in a broader approach and prospect. There is a gap in our knowledge as for how the behavioral repertoire operationalizes "defensive behavior" and that, by inference, how these neural structures somehow "experience" and process aversive input and transduce it into behavioral and vegetative and/or endocrine reactions. The research in this area can be considered in terms not merely of "defensive-aversive behavior" as is often the case, but also in terms of sensory and perceptual aspects related to the incoming aversive stimuli. We are interested in emphasizing the potential relevance of this field of research for understanding aversive event-induced processes, including fear and anxiety, and other related consequent problems, such as stress. The challenge will be to establish an integrative approach (behavioral, pharmacological, eletrophysiological, neurochemcial and imunohistochemical) that enable us to characterize the whole stimulus-defensive behavior process instead of treating the defense reaction in relative isolation, and secondly, the neurochemical and anatomical systems that subserve the consequences of aversive information to the organism so as to produce knowledge that might lead to therapeutic change using novel behavioral and drug therapy. (AU)
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