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In brief serotonin can interact with
In brief, serotonin can interact with 7 classes of receptors are differentiated into 14 subtypes (Barnes and Sharp, 1999). Specifically, 5-HT1A and 5-HT2C receptors have been the most widely studied in the modulation of anxiety responses (Deakin et al., 1992; Millan, 2003). However, the studies that have investigated the role of serotonin in pain modulation have reported inconsistent results (Sommer and Kress, 2004; Sommer, 2006).
The 5-HT1A, an inhibitory G-coupled protein receptor (GCPR), and 5-HT2C, a stimulatory GCPR (Azmitia, 2007; Pytliak et al., 2011; Shih et al., 1991), are widely distributed in ruthenium red regions involved in defensive behaviors, including the amygdala (Pompeiano et al., 1994; Hannon and Hoyer, 2008; Artigas, 2013). In this context, previous studies have emphasized the role of the amygdala 5-HT1 and 5-HT2 receptors in the modulation of defensive responses. Specifically, intra-amygdala injection of 8-OH-DPAT (a 5-HT1A receptor agonist) elicits anxiogenic-like effects but fails to alter OAA responses (Nunes-de-Souza et al., 2000). Regarding the involvement of 5-HT2 receptors located in the amygdala on defensive responses, local injections of 5-HT2C agonists have induced anxiogenic-like effects in rats (Vicente and Zangrossi, 2012; de Melo Cruz et al., 2005; Christianson et al., 2010).
In the last two decades, there has been an increasing interest to investigate the interaction between serotonergic receptors and SSRIs. In this context, previous findings have suggested that SSRIs can change the anxiolytic effects induced by intracerebral injections of serotonergic agonists in rats (de Bortoli et al., 2006; Vicente and Zangrossi, 2012, 2014; Zanoveli et al., 2007, 2010). However, it remains to be determined whether fluoxetine is capable to change the effects of 5-HT1A and 5-HT2C receptor activation in the amygdaloid complex on nociception.
Thus, it is relevant to evaluate the role of the amygdala 5-HT1A and 5-HT2C receptors in OAA, as well as to investigate whether fluoxetine can alter the effects of intra-amygdala injections of 5-HT1A or 5-HT2C agonists on this type of defensive response. Thereby, our hypothesis is that fluoxetine can change the effects of intra-amygdala injections of 5HT1A or 5HT2C receptor agonists on OAA. To study that, we investigated the effects of (i) intra-amygdala injections of 8-OH-DPAT, a 5-HT1A receptor agonist, (ii) the combined systemic fluoxetine and intra-amygdala injections of 8-OH-DPAT, (iii) intra-amygdala injections of MK-212, a 5-HT2C receptor agonist, (iv) the combined systemic fluoxetine and intra-amygdala injections of the MK-212, and (v) the combined intra-amygdala injections of SB-242084 (a 5-HT2C antagonist) and MK-212 on EPM-OAA in mice.
Material and methods
Results
Only mice with microinjection sites located bilaterally within the amygdala were included in the study. Histological analysis confirmed that 338 mice had accurate microinjection the amygdala. Cannula placements were within the basolateral nucleus (60%), the lateral nucleus (14%), the central nucleus (12%) and in the basomedial nucleus (14%) of the animals. The following groups were formed: 66 animals were used to investigate the effects of intra-amygdala microinjection of 8-OH-DPAT (vehicle, 5.6 or 10 nmol) (Exp1). In experiment 2, 78 mice were used to evaluate the effects of systemic fluoxetine (2.5 mg/kg s. c.) and intra-amygdala injections of 8-OH-DPAT (10 nmol). 65 mice were used to assess the effects of intra-amygdala microinjections of MK-212 (vehicle, 0.21 or 0.63 nmol) in experiment 3. In experiment 4, 76 mice were necessary to reveal the effects of systemic fluoxetine (2.5 mg/kg s. c.) and intra-amygdala microinjections of MK-212 (0.63 nmol). In experiment 5, 53 mice were required to reveal the effects of intra-amygdala microinjections of SB-242084 (0.1 nmol) and intra-amygdala microinjection of MK-212 (0.63 nmol). The sample sizes for each experimental group are shown in Table 1.