Endocannabinoid, opioids peptides and serotonina neural systems interaction into dorsomedial portion of hypothalamus ventromedial on the innate defensive responses of guinea pigs confronted with Snakes.

• Grant number: 12/05824-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2012
• End date: February 28, 2014
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Norberto Cysne Coimbra
• Grantee: Mateus Dalbem Ferreira
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Evidence has shown that endocannabinoids and CB1 receptors are involved in various emotional disorders, including anxiety and depression. The interaction of encocannabinoid system with others neurotransmitters such as endogenous opioids peptides and serotonin (5-HT) has also been subject of several studies, since the increase of activity of this system promotes anxiolytic and antidepressant responses. Some neural substrates have an important role in the emotional disorders treatment. Hypothalamus is a structure that modulates both behavioral responses involved in emotions, and physiological responses. Some studies showed that the portion of the ventromedial hypothalamus modulates defensive responses such as escape and tonic immobility, responses elicited by animals in situations of innate fear in a confrontation with a predator. Within this perspective, this study aims to evaluate the effect of acute and chronic treatment with fluoxetine, a drug used as an antidepressant and panicolitic activity, cannabidiol a CB1 receptor agonist, and 5-HT1A receptors, on defensive and neurovegetative responses defensive in guinea pigs (Cavia porcellus) raised on a natural predator a snake Boa constrictor amarali. Animals are treated for 21 days with serotonin reuptake inhibitor, with cannabidiol or vehicle (saline or saline + DMSO). The rodents on fourteenth to twentieth day of chronic treatment will be submitted to a habituation to the arena provided with artificial burrows. In the twenty-first day of treatment the animals will be placed in the arena containing the predator and the instinctive responses of defense immobility (freezing), explosive escape and escape directed to borrow, and soon after, tonic immobility response, in the same time te neurovegetative responses will be registred (blood pressure). We will also made intradiencefalic microinjection of AM251 (CB1 receptor antagonist), CTPO (µ-opioid antagonist), WAY100635 (5-HT1A antagonist), saline and saline + DMSO in different groups of mice after chronic treatment with fluoxetine, cannabidiol, saline or saline + DMSO on the defensive and neurovegetative responses evoke by the predator. Finally, it is checked a 5-HT, cannabinoid and opioidergic co-transmission on dorsomedial ventromedial hypothalamus portion on guinea pigs, using immunohistochemistry technique. Finally, we will evaluate the Fos protein expression in the medial amygdaloid nucleus, dorsomedial hypothalamic ventromedial portion in pre-mammillary nucleus of the hypothalamus, anterior hypothalamus and in the various columns of the periaqueductal gray region of guinea pigs subjected to the various pharmacological treatments in the presence the natural predator.