Abstract

We investigated the role of angiotensin II type 1 (AT1 receptor) and type 2 (AT2 receptor) and MAS receptors present in the medial amygdaloid nucleus (MeA) in behavioral changes in the forced swimming test (FST) evoked by acute restraint stress in male rats. For this, rats received bilateral microinjection of either the selective AT1 receptor antagonist losartan, the selective AT2 receptor antagonist PD123319, the selective MAS receptor antagonist A-779, or vehicle 10 min before a 60 min restraint session. Then, behavior in the FST was evaluated immediately after the restraint (15 min session) and 24 h later (5 min session). The behavior in the FST of a non-stressed group was also evaluated. We observed that acute restraint stress decreased immobility during both sessions of the FST in animals treated with vehicle in the MeA. The decreased immobility during the first session was inhibited by intra-MeA administration of PD123319, whereas the effect during the second session was not identified in animals treated with A-779 into the MeA. Microinjection of PD123319 into the MeA also affected the pattern of active behaviors (i.e., swimming and climbing) during the second session of the FST. Taken together, these results indicate an involvement of angiotensinergic neurotransmissions within the MeA in behavioral changes in the FST evoked by stress.

Highlights

  • Available pharmacological treatments for depression are only partially effective as the remission rate is only 30% for patients treated with the traditional therapy, so that new pharmacological targets for depression treatment have been explored [1,2]

  • In the present study we evaluated the role of angiotensin II type 1 (AT1), angiotensin II type 2 (AT2) and MAS receptors present in the medial amygdaloid nucleus (MeA) in behavioral changes in the forced swimming test (FST) evoked by an acute session of restraint stress in rats

  • Results reported in the present study provide the first evidence of an involvement of MeA angiotensinergic neurotransmission in behavioral changes evoked by aversive threats

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Summary

Introduction

Available pharmacological treatments for depression are only partially effective as the remission rate is only 30% for patients treated with the traditional therapy (monoamine pathways alterations), so that new pharmacological targets for depression treatment have been explored [1,2]. Studies in rodents revealed that exposition to acute stressors led to alterations in depression-like behavioral in several tasks, including the forced swimming test (FST) [4,5,6,7]. Despite these pieces of evidence, the neurobiological mechanisms involved in behavioral changes evoked by stressful stimuli are not completely understood. The effects of angiotensin-(1–7) are mainly mediated by activation of the MAS receptor [9,10,11]

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