|Support type:||Scholarships in Brazil - Master|
|Effective date (Start):||September 01, 2009|
|Effective date (End):||October 31, 2010|
|Field of knowledge:||Biological Sciences - Pharmacology - Neuropsychopharmacology|
|Principal researcher:||Norberto Cysne Coimbra|
|Grantee:||Andres Uribe Marino|
|Home Institution:||Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil|
The encephalic aversion system is composed of different mesencephalic and prosencephalic structures such as the periaqueductal gray matter, deep layers of the superior colliculus, central nucleus of the inferior colliculus, amygdala and medial hypothalamus. These areas constitute the main neural substrate for the integration of aversive states in the central nervous system. Thus, chemical and electrical stimulation procedures of brainstem regions elicit explosive defensive responses related to fear and similar to those exhibited by patients with panic disorder. However, analogous techniques applied in different medial hypothalamic nuclei produce less intense and more organized escape behaviors. Generally, after stimulation of these structures, antinociceptive processes are observed which are modulated by several chemical substances of opioid and non-opioid nature in midbrain and some nuclei of the pain inhibitory endogenous system and hypothalamic complex regulated by inhibitory GABAergic projections.The objective of the present research project consists in the establishment of connections between ventro-medial hypothalamus (VMH) and dorso-medial hypothalamus (DMH) with monoaminergic nuclei of the pain inhibitory endogenous system , such as the dorsal raphe nucleus (DRN) and Locus coeruleus (LC), through a neuroanatomical study with iontophoretic microinjections of an anterograde and retrograde neurotracer, Biodextran combined with Texas Red or fluorescein in each hypothalamic nuclei studied, followed by inmunohistochemical reactions for the identification of positive neurons for Tyrosine Hydroxylase. Another study will be made on the effects of the neurotoxic lesion with specific neurotoxins for noradrenergic neurons in the LC, that possibly have direct or indirect connections with VMH and DMH and have some role in the analgesia induced by evoked fear after the chemical stimulation of the VMH and DMH. In independent groups of animals, the effects of pre-treatment with microinjections of noradrenergic antagonists in the DRN will be determined, a structure that posses reciprocal connections with the LC, to evaluate the involvement of the coeruleus-dorsal raphe pathway on pain control during the organization of antinociception induced by oriented escape behaviors.