Orexin 2 receptor stimulation enhances resilience, while orexin 2 inhibition promotes susceptibility, to social stress, anxiety and depression
| Autor: | Fadi Haroun, Tangi R. Summers, Samuel S. Newton, Belissa S. Fernandez, Cliff H. Summers, Bali K. Summers, Monica Sathyanesan, Jazmine D. W. Yaeger, Clarissa D. Staton, Delan Khalid, Jessica S. Fernandez |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Reflex Startle medicine.drug_class Stimulation Anxiety Anxiolytic Amygdala Article 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Orexin Receptors Internal medicine Conditioning Psychological medicine Animals Fear conditioning Freezing Reaction Cataleptic Social Behavior Pharmacology Social stress Neurons Orexins Psychotropic Drugs business.industry Aggression Depression Fear Resilience Psychological Orexin Mice Inbred C57BL 030104 developmental biology Endocrinology medicine.anatomical_structure Orexin Receptor Antagonists medicine.symptom business 030217 neurology & neurosurgery Stress Psychological Basolateral amygdala |
| Zdroj: | Neuropharmacology. 143 |
| ISSN: | 1873-7064 |
| Popis: | 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 icv 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect