Effects of the antagonist on the 5-HT1A receptors in ventral hippocampus on anxiety - and panic - related defensive behaviors

Abstract

Little is known about the serotonergic activity in the Ventral Hippocampus (VH) and the regulation of different subtypes of anxiety. A former study done in our laboratory, using the elevated T maze (ETM) has shown that the activation on 5-HT1A receptors on the VH has decreased the animal's avoiding behavior with no effects over the escape behavior, resembling to what was observed in the result of the action of midazolam over de GABAA receptor. This indicates a role of those receptors in the regulation of the Generalized Anxiety Disorder, but not over the Panic Disorder. However, it hasn't been verified yet the direct effect of serotonin on the VH on manifestations of this subtypes of anxiety on the ETM; as it hasn't been done a rate-response curve of the antagonist of the receptor of 5-HT1A Way 100,635 on the hippocampus' area in relation to the presentation of defensive avoiding and escaping behaviors on this experimental model. This way, our goal with this study is to investigate this aspects. Male Wistar mice will be submitted to stereotactic surgery for cannula implant, allowing the bilateral access to the Ventral Hippocampus. To accustom the animals to the researcher, on the 4th and 5th post-surgery day, the animals will be submitted to "handling" (5 minutes per day). On the 6th post-surgery day, the mice will be restricted to the open wings of the Elevated T Maze for 30 minutes. Twenty-four hours after the restriction the mice will be submitted to a behavior evaluation on the Elevated T Maze and right after will be put on the arena (on the 7th post stereotactic surgery day), immediately after the bilateral Ventral Hippocampus microinjections. The study will be developed in two steps, which one of the steps will have a control group with saline microinjections on the VH. Each group will be constituted by the minimum of 10 animals. 1st step - microinjection of serotonin on the VH (4, 8 or 16 nmol - 5-Hydroxytryptamine hydrochloride); 2nd step - microinjections of the specific antagonist of the 5-HT1A Way 100,635 receptors (0,18 nmol; 0,37 nmol and 0,74 nmol). The results will be submitted to Anova of repeated measures, evaluating separately the Avoiding and Escaping behaviors on the ETM, as well the number of squares wandered on the arena, as an index of motor activity of animals, comparing the treatments (used solutions and underdosing) and the re-expositions of each wing of ETM, in each step of the study separately. The results here found will propitiate subsidies to the continuity of this study which will verify if the anxiolytic effect of fluoxetine could also be related to the function of the 5-HT1A receptor on the VH through the previous antagonizing of these receptors after the chronic treatment of this drug.