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Neurobiology of stress: the sensorimotor gating

Grant number: 11/00041-3
Support type:Research Projects - Thematic Grants
Duration: August 01, 2011 - July 31, 2015
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Marcus Lira Brandão
Grantee:Marcus Lira Brandão
Home Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
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)

Scientific publications (19)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
REIS, FERNANDO M. C. V.; ALMADA, RAFAEL C.; FOGACA, MANOELA V.; BRANDAO, MARCUS L. Rapid Activation of Glucocorticoid Receptors in the Prefrontal Cortex Mediates the Expression of Contextual Conditioned Fear in Rats. CEREBRAL CORTEX, v. 26, n. 6, p. 2639-2649, JUN 2016. Web of Science Citations: 6.
MUTHURAJU, SANGU; TALBOT, TEDDY; BRANDAO, MARCUS LIRA. Dopamine D-2 receptors regulate unconditioned fear in deep layers of the superior colliculus and dorsal periaqueductal gray. Behavioural Brain Research, v. 297, p. 116-123, JAN 15 2016. Web of Science Citations: 7.
REIMER, ADRIANO EDGAR; DE OLIVEIRA, AMANDA RIBEIRO; DINIZ, JULIANA BELO; HOEXTER, MARCELO QUEIROZ; CHIAVEGATTO, SILVANA; BRANDAO, MARCUS LIRA. Rats with differential self-grooming expression in the elevated plus-maze do not differ in anxiety-related behaviors. Behavioural Brain Research, v. 292, p. 370-380, OCT 1 2015. Web of Science Citations: 10.
DE OLIVEIRA, AMANDA RIBEIRO; COLOMBO, ANA CAROLINE; MUTHURAJU, SANGU; ALMADA, RAFAEL CARVALHO; BRANDAO, MARCUS LIRA. Dopamine D-2-Like Receptors Modulate Unconditioned Fear: Role of the Inferior Colliculus. PLoS One, v. 9, n. 8 AUG 18 2014. Web of Science Citations: 9.
DE OLIVEIRA, AMANDA R.; REIMER, ADRIANO E.; BRANDAO, MARCUS L. Mineralocorticoid receptors in the ventral tegmental area regulate dopamine efflux in the basolateral amygdala during the expression of conditioned fear. PSYCHONEUROENDOCRINOLOGY, v. 43, p. 114-125, MAY 2014. Web of Science Citations: 5.
MUTHURAJU, S.; NOBRE, M. J.; SAITO, V. M. N.; BRANDAO, M. L. DISTINCT EFFECTS OF HALOPERIDOL IN THE MEDIATION OF CONDITIONED FEAR IN THE MESOLIMBIC SYSTEM AND PROCESSING OF UNCONDITIONED AVERSIVE INFORMATION IN THE INFERIOR COLLICULUS. Neuroscience, v. 261, p. 195-206, MAR 7 2014. Web of Science Citations: 9.
ALMADA, RAFAEL C.; ALBRECHET-SOUZA, LUCAS; BRANDAO, MARCUS L. Further evidence for involvement of the dorsal hippocampus serotonergic and gamma-aminobutyric acid (GABA) ergic pathways in the expression of contextual fear conditioning in rats. JOURNAL OF PSYCHOPHARMACOLOGY, v. 27, n. 12, SI, p. 1160-1168, DEC 2013. Web of Science Citations: 5.
COLOMBO, ANA CAROLINE; DE OLIVEIRA, AMANDA RIBEIRO; REIMER, ADRIANO EDGAR; BRANDAO, MARCUS LIRA. Dopaminergic mechanisms underlying catalepsy, fear and anxiety: Do they interact?. Behavioural Brain Research, v. 257, p. 201-207, NOV 15 2013. Web of Science Citations: 8.
GENARO, KARINA; JULIANO, MARIA A.; PRADO, WILIAM A.; BRANDAO, MARCUS L.; MARTINS, ANTONIO R. Effects of angiotensin (5-8) microinfusions into the ventrolateral periaqueductal gray on defensive behaviors in rats. Behavioural Brain Research, v. 256, p. 537-544, NOV 1 2013. Web of Science Citations: 2.
DE SOUZA CAETANO, KATIA A.; DE OLIVEIRA, AMANDA R.; BRANDAO, MARCUS L. Dopamine D2 receptors modulate the expression of contextual conditioned fear: role of the ventral tegmental area and the basolateral amygdala. Behavioural Pharmacology, v. 24, n. 4, p. 264-274, AUG 2013. Web of Science Citations: 26.
ALBRECHET-SOUZA, LUCAS; CARVALHO, MILENE CRISTINA; BRANDAO, MARCUS LIRA. D-1-like receptors in the nucleus accumbens shell regulate the expression of contextual fear conditioning and activity of the anterior cingulate cortex in rats. INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, v. 16, n. 5, p. 1045-1057, JUN 2013. Web of Science Citations: 17.
BORELLI, KARINA G.; ALBRECHET-SOUZA, LUCAS; FEDOCE, ALESSANDRA G.; FABRI, DENISE S.; RESSTEL, LEONARDO B.; BRANDAO, MARCUS L. Conditioned fear is modulated by CRF mechanisms in the periaqueductal gray columns. Hormones and Behavior, v. 63, n. 5, p. 791-799, MAY 2013. Web of Science Citations: 8.
CARVALHO, M. C.; SANTOS, J. M.; BASSI, G. S.; BRANDAO, M. L. Participation of NK1 receptors of the amygdala on the processing of different types of fear. NEUROBIOLOGY OF LEARNING AND MEMORY, v. 102, p. 20-27, MAY 2013. Web of Science Citations: 12.
REIMER, A. E.; DE OLIVEIRA, A. R.; BRANDAO, M. L. GLUTAMATERGIC MECHANISMS OF THE DORSAL PERIAQUEDUCTAL GRAY MATTER MODULATE THE EXPRESSION OF CONDITIONED FREEZING AND FEAR-POTENTIATED STARTLE. Neuroscience, v. 219, p. 72-81, SEP 6 2012. Web of Science Citations: 14.
REIS, FERNANDO M. C. V.; ALBRECHET-SOUZA, LUCAS; FRANCI, CELSO R.; BRANDAO, MARCUS L. Risk assessment behaviors associated with corticosterone trigger the defense reaction to social isolation in rats: Role of the anterior cingulate cortex. STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS, v. 15, n. 3, p. 318-328, MAY 2012. Web of Science Citations: 11.
BROIZ, A. C.; BASSI, G. S.; SILVA, M. A. DE SOUZA; BRANDAO, M. L. EFFECTS OF NEUROKININ-1 AND 3-RECEPTOR ANTAGONISTS ON THE DEFENSIVE BEHAVIOR INDUCED BY ELECTRICAL STIMULATION OF THE DORSAL PERIAQUEDUCTAL GRAY. Neuroscience, v. 201, p. 134-145, JAN 10 2012. Web of Science Citations: 5.

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