Effect of midazolam in ventral hippocampus on anxiety manifestation in the Elevated T maze

Abstract

This study aims to investigate the involvement of the ventral hippocampus (VH) on manifestation of generalized anxiety and panic, by assessing the activity of GABA A receptors in this structure. For this purpose, male Wistar rats will undergo stereotactic surgery to implant cannulas, enabling access to the ventral hippocampus bilaterally. In the 4th and 5th postoperative days, the animals will be subjected to handling for the habituation to researcher (5 minutes/day). On the 6th day after the surgery the rats will be confined in one of the open arms of the ETM maze, for 30 minutes. The animals will be evaluated in the ETM, twenty-four hours after the confinement procedure and, in sequence, in open field (on the 7th day after stereotactic surgery. Immediately after the microinjections in the Ventral Hippocampus (Control group - saline; Experimental groups: Midazolam (10, 20 or 40nmol) - GABA A agonist) each animal will be put in the end of the closed arm of the ETM. After the behavioural assessment, the animals will euthanized by lethal overdose of anesthetic for the perfusion with saline and formaldehyde at 10% aiming to identify the site of microinjection. The latencies of inhibitory avoidances or escapes will be subjected to analysis of variance for repeated measures (ANOVA) (baseline, avoidance 1, avoidance 2 or escape 1, escape 2 and escape 3). When appropriate, multiple comparisons will be made using the Duncan test. The results of motor activity in the open field will be analyzed using ANOVA. In all cases a p-value less than 0.05 will considered significant.