(534.9) Role of CRF1 and CRF2 receptors in the lateral hypothalamus in anxiogenic response evoked by acute and repeated restraint stress in rats

Poster Board Number: B40

Lucas de Souza (School of Pharmaceutical Sciences, São Paulo State University (UNESP), Joint Graduate Program in Physiological Sciences (PIPGCF), UFSCar/UNESP), Lilian Liz Silva (School of Pharmaceutical Sciences, São Paulo State University (UNESP), Postgraduate Program in Pharmaceutical Sciences), Carlos Crestani (School of Pharmaceutical Sciences, São Paulo State University (UNESP), Joint Graduate Program in Physiological Sciences (PIPGCF), UFSCar/UNESP)

The lateral hypothalamus (LH) is an important hypothalamic area that has been implicated in the integration of behavioral and physiological responses to stress. The corticotropin-releasing factor (CRF) system has been shown to be an important neurochemical mechanism in the central nervous system involved in the etiology of the behavioral changes evoked by exposure to aversive situations. The exposure to chronic stress affects the expression of CRF neurotransmission components in brain regions controlling stress responses. However, the role of CRF neurotransmission within the LH in the anxiogenic responses evoked by acute and repeated restraint stress (RS) has not been investigated. Here, was investigated the effect of bilateral microinjection into the LH of the selective CRF1 receptor antagonist CP376395 or the selective CRF2 receptor antagonist antisauvagine-30 (ASV-30) in the anxiogenic responses following the first and the 10th session of restraint stress (RS) in male rats. For this, male Wistar rats (250g) had cannula-guide bilaterally implanted within the LH. The RS was realized by placing the animals in a plastic cylindrical tube for 60 minutes. Independent sets of animals received CP376395 (0.01 mol/100nL), ASV-30 (0.01 mol/100nL) or vehicle into the LH 10 minutes before the onset of the first or 10th session of RS. Immediately after the end of the stress session, the animals were individually placed in the elevated plus maze (EPM) for 5 minutes to assess anxiety-related behaviors. The behavioral analysis revealed that an acute RS session decreased the % of entries and time in the open arms of the EPM in vehicle-treated animals, when compared to animals that were not submitted to restraint stress (i.e., naïve group) (Plt;0.05). Bilateral microinjection of either CP376395 or ASV-30 into the LH inhibited the decreased open-arms exploration caused by acute restraint stress (Plt;0.05). We did not identify behavioral changes in the EPM in animals repeatedly subjected to restraint stress, and pharmacological treatments also had no behavioral effect when administered before the 10th RS session (Pgt;0.05). Taken together, the results indicates that the CRFergic neurotransmission in the LH, acting through activation of both CRF1 and CRF2 receptors, is involved in the generation of anxiety-like behaviors induced by acute restraint stress, and the previous repeated exposure to this stressor affect this control.

FAPESP: namp;amp;[ordm] 2018/14284-4