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  • As shown in a previous report Donatti and Leite Panissi

    2020-07-30

    As shown in a previous report (Donatti and Leite-Panissi, 2011), microinjection of CRF into the BLA or CeA of the guinea pig increased the duration of TI episodes compared to control episodes (Fig. 2A–D). However, when the microinjection of CRF into the BLA or CeA was preceded by the injection of CP-376395 (0.4 μg) or ASTR 2B (0.4 μg) into these areas, the effect of CRF was blocked. A repeated-measures ANOVA revealed a significant difference between treatments (F6,27 = 6.03, P < 0.05; F5,23 = 8.482, P < 0.005, into the BLA and CeA, respectively) when CRF was preceded by the CRF1 AC220 inhibitor antagonist (CP-376395). A Newman-Keuls post hoc test demonstrated that the treatment with CRF differed (P < 0.05) from the control, sham and CP-376395 + CRF treatments in the BLA (Fig. 2A) and CeA (Fig. 2C). However, there was no difference between the control, sham and CP-376395 + CRF treatments in these areas. Similarly, a repeated-measures ANOVA revealed a significant difference between treatments (F6,27 = 3.630, P < 0.05; F5,23 = 8.430, P < 0.02, into the BLA and CeA, respectively) when CRF was preceded by the CRF2 receptor antagonist (Astressin 2B). A Newman-Keuls post hoc test showed that the treatment with CRF differed (P < 0.05) from the control, sham and ASTR 2B + CRF treatments in the BLA (Fig. 2B) and CeA (Fig. 2D). No differences were observed among the control, sham and ASTR 2B + CRF treatments in both areas. Finally, unilateral microinjection of CP-376395, Astressin 2B, CP-376395 + CRF or ASTR 2B + CRF into the BLA (Fig. 3A) or CeA (Fig. 3B) did not significantly alter spontaneous motor activity in the open field test (F4,24 = 0.148, P > 0.05; F4,29 = 0.290, P > 0.05 in the BLA and CeA, respectively, ANOVA) compared with the guinea pigs that received saline microinjections into the BLA or CeA. Fig. 4 illustrates the sites of the microinjections made in the BLA and CeA for all experimental groups, as well as nearby sites where drugs had no effect.
    Discussion The major finding of the study is that the modulation of fear and anxiety mediated by the CRF system in the BLA and CeA occurs through concomitant effects on CRF1 and CRF2 receptors.In details, the blockade of CRF1 and CRF2 receptors in the BLA and CeA produces a decrease in fear and/or anxiety, as suggested by decreased TI duration in guinea pigs. This decrease does not appear to be due to a modification of spontaneous motor activity, which may affect TI duration nonspecifically. Additionally, antagonists for CRF1 and CRF2 receptors were able to prevent the increase in TI duration induced by CRF administration at the same sites. TI behavior is an innate response triggered by sensorial stimuli and intense fear (Klemm, 2001, Ratner, 1967). This unconditioned response occurs in a wide range of species, included humans (Volchan et al., 2011), and has served as a model to study anxiety and depression (Fiszman et al., 2008, Lima et al., 2010, Olsen et al., 2002, Rocha-Rego et al., 2009). From mesophyll perspective, previous studies have shown that the activation of CRF receptors in the BLA promotes an increase in related responses to fear and anxiety (Sajdyk et al., 1999); the same occurs in the CeA (Skórzewska et al., 2009), including an increase in TI response in guinea pigs (Donatti and Leite-Panissi, 2011). Together, these results suggest that an increase of CRF release in the amygdala and the activation of CRF receptors serve as a neural substrate for fear-like reactions (Sajdyk and Gehlert, 2000, Skórzewska et al., 2009).