Journal
NEUROPHARMACOLOGY
Volume 143, Issue -, Pages 79-94Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2018.09.016
Keywords
Anxiety; Defeat; Depression; Fear conditioning; Freezing; Hypocretin; Resilience; Susceptibility; Startle; Stress Alternatives Model
Categories
Funding
- National Institute of Mental Health of the National Institutes of Health [R15MH104485, R01MH106640]
- CBBRe Research Enhancement Pilot grant
Ask authors/readers for more resources
Knockdown of orexin/hypocretin 2 receptor (Orx(2)) in the basolateral amygdala (BLA) affects anxious and depressive behavior. We use a new behavioral paradigm, the Stress Alternatives Model (SAM), designed to improve translational impact. The SAM induces social stress in adult male mice by aggression from larger mice, allowing for adaptive decision-making regarding escape. In this model, mice remain (Stay) in the oval SAM arena or escape from social aggression (Escape) via routes only large enough for the smaller mouse. We hypothesized intracerebroventricular (icv) stimulation of Orx(2) receptors would be anxiolytic and antidepressive in SAM-related social behavior and the Social Interaction/Preference (SIP) test. Conversely, we predicted that icy antagonism of Orx(2) receptors would promote anxious and depressive behavior in these same tests. Anxious behaviors such as freezing (both cued and conflict) and startle are exhibited more often in Stay compared with Escape phenotype mice. Time spent attentive to the escape route is more frequent in Escape mice. In Stay mice, stimulation of Orx(2) receptors reduces fear conditioning, conflict freezing and startle, and promotes greater attention to the escape hole. This anxiolysis was accompanied by activation of a cluster of inhibitory neurons in the amygdala. A small percentage of those Stay mice also begin escaping; whereas Escape is reversed by the Orx(2) antagonist. Escape mice were also Resilient, and Stay mice Susceptible to stress (SIP), with both conditions reversed by Orx(2) antagonism or stimulation respectively. Together, these results suggest that the Orx(2) receptor may be a useful potential target for anxiolytic or antidepressive therapeutics.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available