Participação do sistema glutamatérgico da substância cinzenta periaquedutal dorsolateral na resposta defensiva de ratos submetidos ao teste-reteste no labirinto em cruz elevado

Abstract

The elevated plus-maze (EPM) has been widely used as a tool to understand defensive behavior related to anxiety. Prior EPM experience alters behavioral and pharmacological responses elicited in a subsequent test exposure (retest). EPM-experienced rodents no longer respond to anxiolytics and increase open arm avoidance (OAA) in retest to EPM. This qualitative shift in the defensive responses evocated during retest has proven to be suitable to assess aspects related to learning/memory and anxiety. In addition, this shift may be related to different sets of brain structures being preferentially involved in the expression of fear/defensive behaviors during test and retest in EPM. The dorsal periaqueductal gray (dPAG) is a neural structure known to be involved in the modulation of defensive behavior in EPM. In addition, lesion studies have shown its participation in the acquisition and the expression of learned defensive responses. Based on these facts, the main aim of this study was to verify the role of glutamate acting compounds microinjected into the dPAG in the performance of rats during the test and the retest in the EPM and the participation of dPAG in acquisition, consolidation and retrieval to fear conditioning in Step-down inhibitory avoidance task (SD). For this purpose, male Wistar rats received microinjections (0.3 ìl) through the guide cannulas aiming at the dPAG: PBS (control), AP5 (3 e 6 nmol, receptor competitive NMDA antagonist) or ifenprodil (0,5 e 1 nmol, receptor subunit NR2B selective NMDA antagonist), 10 min, prior to test and retest (24h after test) in the EPM. One week later, the subjects# dPAG was blocked with AP5 and Ifen prior/aftertest and prior-retest in SD. The results show that the blockade of the dPAG with the competitive NMDA antagonist or the selective NR2B NMDA subunit receptor antagonist increased the exploration on open arms. This effect is related to anxiolytic-like behavior in rats during the test in EPM. The microinjection of competitive or selective NR2B NMDA subunit receptor antagonists in the dPAG increased the exploratory activity in open arms during the retest, preventing the expression of avoidance to open arms in a subsequent test exposure to EPM. However, repeat treatment with AP5 3 nmol and Ifenprodil 1 nmol before the test and retest in EPM induce to anxiolytic effect tolerance during the retest. The blockade of the dPAG with the competitive NR2 or the selective NR2B, NMDA subunit receptor antagonists impairs the expression of the acquired inhibitory avoidance but is not capable in interfering the acquisition or the consolidation in the SD. In conclusion, our results reinforce that glutamate system, through NMDA receptor, is involved in behavior like-anxiety. Moreover, the results demonstrate that the blockade of NMDA receptors in the dPAG impair the retrieval of learning response during the test, in both, in EPM and in inhibitory avoidance test. The present study suggest that the dPAG is a fundamental structure in the expression of defensive behavior showed toward threaten stimulus, and also is involved in the process of retrieval learning defensive response.