Date of Award

Spring 4-27-2022

Document Type

Honors Thesis



First Advisor

Cliff H. Summers

Second Advisor

Beate Wone

Third Advisor

Brian Burrell


orexin, social stress, hypocretin, stress alternatives model, anxious behavior

Subject Categories

Medical Neurobiology | Neurosciences


Human men and women react to stress in different ways, both biologically and psychologically (Verma et al., 2011). Orexins (or hypocretins) are neuropeptides involved in eliciting a stress response and have been shown to have opposing actions via two different receptors. Activation of the Orx1 receptor promotes stress, while activation of the Orx2 receptor relieves stress (Staton et al., 2018). Using the Stress Alternatives Model (a four-day paradigm in which small female mice are in an open arena with a larger aggressor mouse), distinct phenotypic behaviors can be observed after the second day: anxiety-prone and stress-resilient. After the second day, animals will commit to one specific phenotype. Using an Orx2 receptor antagonist (MK-1064) and an α2 receptor antagonist (yohimbine), phenotypic behavior can change even after mice have committed to a specific phenotype, as late as the third day. It has been shown that the behavioral state of an animal, either anxiety-prone or stress-resilient, can affect the number of neurons containing the orexin peptide (James et al., 2020). We hypothesize that the stress-resilient mice will show more Orx2-containing neurons in the basolateral amygdala (BLA). We examined the number of cells in the BLA containing Orx2 receptors and determined the peptide cell markers that define this receptor action. The neuropeptides cholecystokinin (CCK) and somatostatin (SOM) were found on a minority of neuronal cells in the BLA. CCK can either be glutamatergic or GABAergic, while SOM is one type of GABAergic cell in the BLA. The inhibitory effects of GABAergic cells reduce stress, while excitatory glutamatergic cells promote stress. Orx2 receptors are primarily found in GABAergic neurons that contain CCK, and the number of cells with these receptors are not significantly different between males and females, both before and after anxiogenic drug treatment. It is possible, however, that the number of receptors on each cell increased in number.



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