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  • Some clinical reports have suggested

    2021-09-30

    Some clinical reports have suggested that galanin has a role in the neurobiology of mood disorders [[6], [7], [8], [9], [10]]. In behavioral studies, contradictory results have been reported [11,12]. For example, systemic administration of non-selective galanin receptor agonists, such as galmic [13] and galnon [14], decreased immobility time in rats submitted to the forced swimming test (FST). In contrast, i.c.v. galanin administration increased immobility time in rats tested in the same procedure [15,16], suggesting a depressive-like effect. These contradictory results may be explained by the fact that galanin effects are mediated by different receptors depending on Psalmotoxin 1 regions. Supporting this hypothesis, i.c.v. infusion of a GAL2 (AR-M1896) or a GAL1 (M617) agonist induced antidepressant-like or depressive-like effect, respectively, in rats exposed to the FST [3]. Further, galanin administered in the rat ventral tegmental promoted a depressive-like effect [17]. Notwithstanding, chronic treatment with selective serotonin reuptake inhibitors increased galanin mRNA expression in the ventral hippocampus [18,19], in the amygdala [18] and in the DRN [14,20]. The DRN express both GAL1 [21] and GAL2 receptors [5]. Galanin and serotonin co-exist in almost 40% of DRN neurons [21]. Injection of galanin in the DRN reduces the firing rate of 5-HT neurons [22]. Despite the aforementioned evidence, it is not yet known how intra-DRN galanin would affect behavioral responses to stress in models that are predictive of antidepressant-like effects. Therefore, we investigated herein if the infusion of galanin in the DRN would affect immobility time in the FST, an animal model with good predictability for antidepressant-like effect [23]. We also investigated the effects induced by the infusion of selective galanin receptor agonists in the DRN of rats tested in the same paradigm to characterize the mechanism involved in galanin-induced antidepressant-like effect. Finally, to confirm the involvement of GAL2 receptors on galanin-induced effects in the DRN, we evaluated if the previous infusion of a selective GAL2 antagonist in the DRN would counteract galanin effects.
    Material and methods
    Discussion Our results showed that the infusion of a low dose of galanin (0.3 nmol) in the DRN reduced the immobility time of rats submitted to the FST, suggesting an antidepressant-like effect. A similar effect was observed with the administration of the GAL2 agonist, AR-M1896, but not with the administration of the GAL1 agonist, M617. Consistent with those results, galanin effect was blocked by previous administration of the GAL2 antagonist, M871. Altogether, our data suggest that galanin signaling in the DRN mediates antidepressant-like effects through activation of GAL2 receptors. Galanin dose used herein was chosen based on a previous study from our laboratory showing that it was able to induce anxiolytic-like effects, whereas a higher dose (1.0 nmol) increased locomotor activity in the open field test [24]. The antidepressant-like effect induced by intra-DRN galanin administration corroborates with other studies showing that systemic administration of non-peptide ligands of galanin reduced immobility time in the FST [13,14]. In contrast, some studies showed that i.c.v. galanin administration in higher doses produced depressive-like effects [3,15,16]. It is worth noting that after i.c.v. infusion, galanin diffuses to the periventricular zone, hippocampus [28] and amygdala [29] but no galanin immunoreactivity labeling of cells was seen at the level of the DRN [29]. Thus, the depressive-like effect induced by galanin through intracerebroventricular infusion might not be due to activation of galanin receptors in the DRN. It has been reported that DRN neurons express at least two galaninergic receptors, GAL1 and GAL2 [5,21]. In an attempt to determine which galanin receptor would be involved in the antidepressant-like effect induced by galanin infusion in the DRN, we administered a GAL1 or a GAL2 agonist in the DRN of rats evaluated in the FST. Infusion of M617, the GAL1 agonist, did not change the immobility time of rats in the FST. In contrast, intra-DRN infusion of AR-M1896, the GAL2 agonist, reduced immobility time in the same procedure. The antidepressant-like effect of AR-M1896 or the lack of effect of M617 do not seem to be caused by locomotor activity facilitation or impairment, since neither M617 nor AR-M1896 infusion in the DRN affected locomotion in the open field test.