Serotonergic activity in ventral hippocampus on 5-HT2C receptors in the regulation of the defensive behaviours related to generalized anxiety and panic

• Grant number: 16/16014-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2016
• Effective date (End): October 31, 2017
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Telma Goncalves Carneiro Spera de Andrade
• Grantee: Mariane Cariati Tirapelle
• Host Institution: Faculdade de Ciências e Letras (FCL-ASSIS). Universidade Estadual Paulista (UNESP). Campus de Assis. Assis , SP, Brazil

Abstract

The serotoninergic activity on 5-HT1A receptors in the ventral hippocampus in the regulation of different types of anxiety is still unknown yet. A previous study in our laboratory using the elevated T maze (ETM) showed that activation of 5 -HT1A receptors in HV decreased avoidance behavior of animals without affecting the escape responses, similar to what was observed as a result of midazolam's action on GABAA receptors, indicating an involvement of these receptors in the regulation of Generalized Anxiety Disorder, but not panic disorder. However, the direct effect of the serotonin on VH has not been verified already, and the activation of serotonergic 5 -HT2C this region of the hippocampus over the manifestation of these anxiety subtypes in ETM have not been evaluated. As well, in order to investigate these aspects, stereotactic surgery to implant cannulae will be done on male Wistar rats, enabling access to the Ventral hippocampus bilaterally. For habituation of animals to the researcher, the 4th and 5th postoperative day, the animals will be submitted to the "handling" (5 minutes / day). On the 6th day after the surgery the rats will be confined in one of the open arms of the ETM for 30 minutes. Twenty-four hours after the confinement the rats will undergo behavioral assessment in the elevated T maze and sequence in the Arena (on the 7th day after stereotactic surgery), immediately after the bilateral microinjection in the hippocampus Ventral. The study will be developed in two steps, and in each one there will be a control group with saline microinjection in HV. Each group will consist of a minimum of 10 animals. Step 1 - microinjection HV Serotonin (4, 8 or 16 nmol - 5-Hydroxytryptamine hydrochloride); Step 2 - microinjection in HV specific agonist of 5-HT2C receptors (MK 212 0.01, 0.1 or 1 nmol - 6-chloro-2-(1-piperazinyl) pyrazine hydrochloride). The results will be submitted to Anova of the repeated measures, evaluating separately the avoidance and escape on ETM, comparing treatments (solutions and doses used) and re-exposure ETM in each arm, at each stage of the study separately. The number of squares covered in the arena, as the index of motor activity of animals, will be evaluated by ANOVA one way.