Involvement of 5-HT1A receptors in the ventral hippocampus in the effect of chronic treatment with fluoxetine on the expression of defensive behaviours related with the generalized anxiety and with the panic

• Grant number: 16/16724-6
• 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: Victor Paschoal Marquezin Nicolli Soares
• Host Institution: Faculdade de Ciências e Letras (FCL-ASSIS). Universidade Estadual Paulista (UNESP). Campus de Assis. Assis , SP, Brazil

Abstract

Yet little is known about the serotonergic activity in the ventral hippocampus (VH) in the regulation of different subtypes of anxiety. Earlier studies performed in our laboratory utilizing the elevated T-maze (ETV) has shown us that the activation of 5-HT1A receptors on the VH decreased the avoidance animals behavior, without affecting the escape response, similar to what was observed as a result of midazolam action on GABAA receptors, indicating involvement of these receptors on the generalized anxiety disorder, but not of the panic disorder. However, still has not been verified the direct serotonin effect in the VH on the manifestation of these subtypes of anxiety in the ETV, as also is not known whether the anxiolytic effect of the fluoxetine is related to the serotonin action on the 5-HT1A receptors in the VH in regarding the presentation of the defensive avoidance behaviors and escape in this experimental model. This study has by objective investigated these aspects. Male Wistar rats will undergo stereotaxic surgery to cannulas implant, enabling access to the ventral hippocampus bilaterally. For the habituation of the animals to the researcher, on the 4th and the 5th postoperative day, the animals will undergo the "handling" (5 minutes/day). On the 6th day after the surgery will be confined in one of the open elevated T-maze arms for 30 minutes. Twenty-four hours after the confinement will undergo behavioral evaluation in the elevated T-maze and in sequence in the arena (on the 7th day after the stereotaxic surgery) immediately after the microinjections bilaterally in the ventral hippocampus, except in the evaluation of the chronic effect of fluoxetine when the microinjections will be done 10 minutes before the last fluoxetine dose. The study will be developed in 2 stages. Stage 1 - VH microinjection of serotonin (4,8 ou 16 nmol - 5-Hydroxytryptamine hydrochloride), having as control animals microinjected with saline in the VH; Stage 2 - Chronic treatment with fluoxetine (10 mg/Kg) for 21 days in a single IP injection and microinjection of the specific antagonist of 5-HT1A receptors Way 100635 (on the dose of 0,18 nmol or 0,37 nmol or 0,74 nmol; the analysis for determining the saline dose of this antagonist will be previously performed by another trainee, in other scientific work of the same research group). In the second stage the following experimental groups will be formed: Group 1 - Saline/Tween80 IP + Saline VH; Group 2 - Saline/Tween80 IP + Way 100635; Group 3 - Fluoxetine + Saline VH; Group 4 - Fluoxetine + Way 100635. Each group will consist of a minimum of 10 animals. The results will be submitted to the analysis of variance of repeated measures, evaluating separately the avoidances and leaks on the ETM, as well the number of squares covered in the arena, as the index of motor activity of the animals, comparing the treatments (solutions and under-doses used) and the expositions again in each of the ETM arms, at each stage of the study separately.(AU)