Orexin signaling during social defeat stress influences subsequent social interaction behaviour and recognition memory

Orexin 2 receptor stimulation enhances resilience, while orexin 2 inhibition promotes susceptibility, to social stress, anxiety and depression

“…The primary thrust of experiments on the orexinergic system relative to affective disorders, has been to describe anxiogenic and pro-depressive actions of Orx A (Eacret et al, 2018; Ito et al, 2009; Lungwitz et al, 2012; Nollet et al, 2011), through actions of Orx 1 receptors (Johnson et al, 2010; Lu et al, 2017; Ozsoy et al, 2017; Staples and Cornish, 2014), although dual Orx receptor antagonists have been shown to be antidepressive (Nollet et al, 2011; Nollet et al, 2012). There have also been hints that Orx 1 and Orx 2 receptors have opposing actions (Flores et al, 2016; Lu et al, 2017), including stress-reduced thalamic and hypothalamic Orx 2 expression that was reversed by the antidepressant fluoxetine (Nollet et al, 2011).…”

“…Not surprisingly, stress reactive orexins play important roles in anxiety, fear, and depression through activation of both Orx receptor subtypes (Abbas et al, 2015; Arendt et al, 2014; Arendt et al, 2013; Eacret et al, 2018; Giardino et al, 2018; Johnson et al, 2015; Johnson et al, 2010; Khalil and Fendt, 2017; Lungwitz et al, 2012; Wang et al, 2017). Intracranial or icv injection of Orx A promotes anxious behavior (Lungwitz et al, 2012; Suzuki et al, 2005), and similar types of anxiogenic (including panic) physiological and behavioral responses can be reversed by blocking Orx 1 receptors (Johnson et al, 2015; Johnson et al, 2010; Staples and Cornish, 2014; Vanderhaven et al, 2015).…”

“…Intracranial or icv injection of Orx A promotes anxious behavior (Lungwitz et al, 2012; Suzuki et al, 2005), and similar types of anxiogenic (including panic) physiological and behavioral responses can be reversed by blocking Orx 1 receptors (Johnson et al, 2015; Johnson et al, 2010; Staples and Cornish, 2014; Vanderhaven et al, 2015). Designer receptor activation of Orx neurons plus antagonism of Orx 2 receptors (Grafe et al, 2017) potentially increases activity only at Orx 1 receptors, or at receptors for Orx-colocalized factors such as glutamate, dynorphin, galanin or nitric oxide (Cheng et al, 2003; Chou et al, 2001; Hakansson et al, 1999; Torrealba et al, 2003), and results in increased anxiety, as well as decreased social interaction and latency to defeat, similar to Orx neuron stimulation alone (Eacret et al, 2018). We have previously suggested that Orx 1 function is diametrically opposed to that of Orx 2 (Arendt et al, 2013).…”

Orexin and Alzheimer’s Disease: A New Perspective

“…[10][11][12] Indeed, a recent study indicated that rats adopted a passive coping behavior after social defeat stress through orexin activation, which induced recognition memory impairments. 13 Orexinergic blockade in the hippocampus reversed stress-induced anxiety behaviors and memory deficits in rats, which suggested potentials of hippocampal orexins as therapeutic targets to minimize stress-induced impairments. 14 A sexual disparity was noted with regard to orexin's role in stress response, a female rat displaying more vulnerability to repeated stress, demonstrating prominent impairments in habituation and cognitive flexibility, with increased orexin expression when compared with male rats.…”

“…With regard to the relationship between orexin and cognition, recent emphasis on orexin’s role as a stress regulator should not be dismissed [ 10 - 12 ]. Indeed, a recent study indicated that rats adopted a passive coping behavior after social defeat stress through orexin activation, which induced recognition memory impairments [ 13 ]. Orexinergic blockade in the hippocampus reversed stress-induced anxiety behaviors and memory deficits in rats, which suggested potentials of hippocampal orexins as therapeutic targets to minimize stress-induced impairments [ 14 ].…”