Midazolam administration after stress exposure prevents the development of a negative emotional state
N.M.Maldonado, I. Martijena, V.A. Molina
Dpto. Farmacología, IFEC-CONICET, FCQ-UNC.
Presentado en IRCN, First Joint Meeting of the Argentine Society for Neuroscience (SAN) and the Argentine Workshop in Neurosciences (TAN). Huerta Grande, Septiembre 4-6 del 2009.
The exposure to threatening stimuli induces exaggerated emotional response related to fear and anxiety in response to a new environmental stimulus, a mechanism defined as Emotional Sensitization.
The Amygdala plays a key role in the processing of aversive information. In fact, the emergence of a negative emotional state has been functionally associated with a reduced GABAergic transmission in this brain area.
We study the effect of MDZ administered after stress in the occurrence of the emotional sensitization assessed by both an associative and a non-associative learning paradigm. Contextual Fear Conditioning (CFC) and Elevated Plus Maze (EPM) were used as associative and non-associative paradigms respectively.
Male Wistar rats (280-300g) were used to perform the experiments. Immediately after a restraint session (30 min), animals were injected with MDZ 1.5mg/Kg,i.p. The formation of fear memory test was evaluated by the freezing response of stressed and control animals, in a paired or in an unpaired context. We observed high freezing levels in stressed animals who were conditioned in the presence of context and footshock contingency. No significant difference among the others groups was detected.
On the other hand, the EPM was performed 24h after the restraint session. The stressed animals injected with VEH (Saline solution) exhibited the typical enhancement of anxiety. In contrast, similar open arm exploration was observed among stressed animals given with MDZ or control animals with VEH or MDZ.
To identify the neuroanatomical substrate involved in this sensitization to the anxiety response, we locally infused MDZ (2ug/ul) or VEH into BLA or into CeA bilaterally, immediately after the stress session. In both areas we observed an anxiety decrease of stressed animals injected with MDZ as compared to the rest of groups.
