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    • br Material and methods br Results

    2018-11-01


    Material and methods
    Results The anxiety-like effects of 8-M-PDOT and 4-P-PDOT treatment, in the EPM are shown in Fig. 2. The sham control 8-M-PDOT increased the percentage of time spent in open arms, compared with the sham control vehicle group (P≤0.01) (Fig. 2A). An increase in this parameter can also be observed after the REMSD in the sham REMSD vehicle group, compared with their respective control (P≤0.001). The rotenone control group remained unchanged. However, REMSD increased the percentage of open arms time as observed in the rotenone REMSD vehicle (P≤0.05) and rotenone REMSD 8-M-PDOT (P≤0.001) groups, compared with their respective controls [F(7,88)=13.26, P<0.001]. The treatment with 4-P-PDOT (Fig. 2B) did not elicit any change in this parameter. However, the only change in percentage of open arms time was as a result of REMSD, observed in the sham REMSD 4-P-PDOT (P≤0.05) and rotenone REMSD 4-P-PDOT (P≤0.001) groups [F(7,91)=14.71, P<0.001]. The treatment with 8-M-PDOT (Fig. 2C) increased the number of open arms entries compared with the respective vehicle group (P≤0.01). The same result is observed in the sham REMSD vehicle group, compared with their respective control group (P≤0.05). Further, the rotenone REMSD 8-M-PDOT (P≤0.001) group presented an increase in this parameter compared with the rotenone control 8-M-PDOT; however the latter group demonstrated a decrease in the number of open arms entries compared to the sham control 8-M-PDOT group (P≤0.05) [F(7,119)=7.050, P<0.0001]. The number of open arms entries was not altered by the 4-P-PDOT treatment (Fig. 2D). Nonetheless, the sham REMSD vehicle group exhibited an increase (P≤0.05) in this parameter compared to the sham control vehicle group [F(7,96)=4.334, P=0.0004]. Fig. 2E depicts the comparisons between treatments of the rotenone groups considering the percentage of time in the open arms. Accordingly, it stearoyl-coa desaturase was not observed significant differences between the 8-M-PDOT and 4-P-PDOT treated groups. In spite of that, only significant increments in the percentage of time in the open arms is observed for the rotenone REMSD 8-M-PDOT and 4-P-PDOT in comparison to their respective rotenone control group [F(3,48)=8.510, P=0.0001]. Likewise, the same type of analysis has been performed for the open arms entries (Fig. 2F), indicating a similar result, with only the increase of this parameter for the rotenone REMSD 8-M-PDOT compared to the rotenone control 8-M-PDOT group [F(3,55)=9.540, P=0.0001]. Fig. 3 shows the effects of 8-M-PDOT and 4-P-PDOT treatment in the locomotion as demonstrated by the OFT. The rotenone REMSD 8-M-PDOT group (Fig. 3A) exhibited an increase in the locomotion compared to their respective vehicle (P<0.01) and control (P<0.001) groups [F(7,76)=7.902, P<0.0001]. Furthermore, neither the treatment with 4-P-PDOT nor the REMSD exposure modified the general activity of the animals (Fig. 3B) [F(7,90)=1.607, P=0.1448]. Once more, the comparisons between treatments of the rotenone groups (Fig. 3C), considering this parameter, demonstrated an increased locomotion in the rotenone control 4-P-PDOT group (P<0.01) compared to the rotenone control 8-M-PDOT group. Additionally, the rotenone REMSD 8-M-PDOT group demonstrated a locomotion increment (P<0.01) compared to the rotenone REMSD 4-P-PDOT group [F(3,38)=12.38, P<0.001].
    Discussion The activation of striatal MT2 receptors by the selective agonist 8-M-PDOT triggered an anxiolytic-like effect, demonstrated, consistently, by the increased percentage of time spent in the open arms and in the number of open arms entries. Conversely, the selective blockade of striatal MT2 receptors, induced by 4-P-PDOT, did not show an anxiogenic-like effect, as assumed. The anxiolytic effects of melatonin in animal models are well described by previous reports [30–32], and more recently, it has been demonstrated the involvement of MT2 receptors in the melatonin anxiolytic-like behavior [39]. The activation of MT2 receptors, by the partial agonist UCM-765, increased the time and entries in the open arms. This effect was blocked by the selective MT2 receptor antagonist, 4-P-PDOT [39]. Thus, anxiolytic-like effect is purportedly associated to MT2 activation. Notwithstanding, in our study we focused on the role of striatal MT2 receptors hence, we investigated if after a dopaminergic degeneration, induced by intranigral rotenone, the administration of MT2 agonist or antagonist would reduce the anxiogenic-like effect of rotenone. In fact, rotenone did not increase the anxiety-like behavior, however this neurotoxin was able to prevent the anxiolytic-like effect promoted by 8-M-PDOT. Another important consideration relies on the time of MT2 drugs infusion (between 7:00a.m. and 9:00a.m.), which is nadir of melatonergic blood levels. Conversely, it is demonstrated that melatonin receptors, in the striatum, did not suffer diurnal variations [49]. Furthermore, it is important to state that our rationale is strictly based on pharmacological activation/blockade of the receptors and not necessarily influenced by the physiological melatonin blood, or brain levels.