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Neurobiology of Behavioral responses to aversive events

Grant number: 98/10639-7
Support type:Research Projects - Thematic Grants
Duration: January 01, 1999 - June 30, 2003
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Francisco Silveira Guimaraes
Grantee:Francisco Silveira Guimaraes
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Co-Principal Investigators:Antonio Waldo Zuardi ; Elaine Aparecida Del Bel Belluz Guimarães


The main objective of the present is to investigate neural systems involved in responses to aversive events. In addition, it will allow the consolidation of research techniques such as immunohistochemistry and in situ hybridization, as well as the introduction of new techniques in our Campus such as in vivo microdialysis. The following studies will be developed: 1) Tole of glutamate and nitric oxide (NO) on responses mediated by the brain aversive system. Behavioral effects of NMDA or NO related drugs, administered into the brain aversive system, will be investigated in animal models of anxiety. In addition, changes in proto-oncogenes and NO synthase will also be studied by immunohistochemistry and in situ hybridization. 2) Effects of manipulations of NMDA/glycine receptors in the dorsal central gay (DCG) in the elevated T-maze test. The role of glutamate neurotransmission in the DCG on anxiety modulation will be investigated in this new model of anxiety. 3) Role of the hipocampal formation on behavioral and neurochemical consequences of stress. Behavioral changes induced by NMDA or NO related drugs, administered into the hippocampus, will be investigated in animal submitted to stress models (immobilization, social isolation). Modifications on NOS, NMDA receptors or APP proteins in this region will also be studied. 4) Experimental tests of the dual hypothesis of the role of serotonin in anxiety using the elevated T-maze test. Pharmacological and biochemical approaches, including immunohistochemistry and in vivo microdialysis techniques, will be employed to investigate the effects of 5HT manipulations in this new model of anxiety. 5) Clinical studies on the role of serotonin in anxiety and the effects of canabidiol (CBD) on psychotic patients. Patients with different forms of anxiety will be submitted to clinical models related to learned or unlearned anxiety. Responses of helathy volunteers submitted to these models under the effect of nefazodone, a serotonin related drug, will also be investigated. In addition, possible anxiolytic and/or antipsychotic effects of a cannabinoid, CBD, will be studied in schizophrenic patients. (AU)

Scientific publications (13)
(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)
CRIPPA‚ J.A.S.; ZUARDI‚ A.W.; BUSATTO‚ G.F.; SANCHES‚ R.F.; SANTOS‚ A.C.; ARAÚJO‚ D.; AMARO‚ E.; HALLAK‚ J.E.C.; NG‚ V.; MCGUIRE‚ P.K. Cavum septum pellucidum and adhesio interthalamica in schizophrenia: an MRI study. EUROPEAN PSYCHIATRY, v. 21, n. 5, p. 291-299, 2006.
M.L.N.M. ROSA; R.C.B. SILVA; F.T. MOURA-DE-CARVALHO; M.L. BRANDÃO; F.S. GUIMARÃES; E.A. DEL BEL. Routine post-weaning handling of rats prevents isolation rearing-induced deficit in prepulse inhibition. Brazilian Journal of Medical and Biological Research, v. 38, n. 11, p. 1691-1696, Nov. 2005.
J.A.S. CRIPPA; R. UCHIDA; G.F. BUSATTO; F.S. GUIMARÃES; C.M. DEL-BEN; A.W. ZUARDI; A.C. SANTOS; D. ARAÚJO; P.K. MCGUIRE; F.G. GRAEFF. The size and prevalence of the cavum septum pellucidum are normal in subjects with panic disorder. Brazilian Journal of Medical and Biological Research, v. 37, n. 3, p. 371-374, Mar. 2004.
R.R. UCHIDA; C.M. DEL-BEN; A.C. SANTOS; D. ARAÚJO; J.A. CRIPPA; F.S. GUIMARÃES; F.G. GRAEFF. Decreased left temporal lobe volume of panic patients measured by magnetic resonance imaging. Brazilian Journal of Medical and Biological Research, v. 36, n. 7, p. 925-929, Jul. 2003.
JOCA‚ S.R.L.; PADOVAN‚ C.M.; GUIMARÃES‚ F.S. Activation of post-synaptic 5-HT1A receptors in the dorsal hippocampus prevents learned helplessness development. Brain Research, v. 978, n. 1, p. 177-184, 2003.
DEL-BEL‚ E.A.; JOCA‚ S.R.L.; PADOVAN‚ C.M.; GUIMARÃES‚ F.S. Effects of isolation-rearing on serotonin-1A and M1-muscarinic receptor messenger RNA expression in the hipocampal formation of rats. Neuroscience Letters, v. 332, n. 2, p. 123-126, 2002.
MOLCHANOV‚ M.; GUIMARÃES‚ F. Anxiolytic-like effects of AP7 injected into the dorsolateral or ventrolateral columns of the periaqueductal gray of rats. Psychopharmacology, v. 160, n. 1, p. 30-38, 2002.
LINO-DE-OLIVEIRA‚ C.; SALES‚ A.J.; APARECIDA DEL BEL‚ E.; SILVEIRA‚ M.C.L.; GUIMARÃES‚ F.S. Effects of acute and chronic fluoxetine treatments on restraint stress-induced Fos expression. Brain Research Bulletin, v. 55, n. 6, p. 747-754, 2001.
C.M. PADOVAN; F.S. GUIMARÃES. Restraint-induced hypoactivity in an elevated plus-maze. Brazilian Journal of Medical and Biological Research, v. 33, n. 1, p. 79-83, Jan. 2000.
DE OLIVEIRA‚ R.M.W.; APARECIDA DEL BEL‚ E.; MAMEDE-ROSA‚ M.L.N.; PADOVAN‚ C.M.; DEAKIN‚ J.F.W.; GUIMARÃES‚ F.S. Expression of neuronal nitric oxide synthase mRNA in stress-related brain areas after restraint in rats. Neuroscience Letters, v. 289, n. 2, p. 123-126, 2000.
DE OLIVEIRA‚ R.W.; DEL BEL‚ E.A.; GUIMARÃES‚ F.S. Behavioral and c-fos expression changes induced by nitric oxide donors microinjected into the dorsal periaqueductal gray. Brain Research Bulletin, v. 51, n. 6, p. 457-464, 2000.
M.L. MOLCHANOV; F.S. GUIMARÃES. Defense reaction induced by a metabotropic glutamate receptor agonist microinjected into the dorsal periaqueductal gray of rats. Brazilian Journal of Medical and Biological Research, v. 32, n. 12, p. 1533-1537, Dez. 1999.
R.W. DE-OLIVEIRA; F.S. GUIMARÃES. Anxiolytic effect of methylene blue microinjected into the dorsal periaqueductal gray matter. Brazilian Journal of Medical and Biological Research, v. 32, n. 12, p. 1529-1532, Dez. 1999.

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