Table 1.
Orexin drug treatments for anxious and depressive behaviors
| Drug Description (animal) | Delivery Method | Dose (nmol) | Description of effect on anxious or depressive behavior | Citation |
|---|---|---|---|---|
| OrxA | ||||
| OrxA (mice) | icv | 1 nmol | ↑ Anxiogenic behaviors in LDT & EPM | Suzuki et al., 2005 |
| OrxA (rats) | icv | 10 nmol | ↑ Locomotion, face-washing, grooming, wet-dog shaking | Matsuzaki et al., 2002 |
| OrxA (rats) | iBNST | 3 nmol | ↑ Anxious behavior in SIP & EPM | Lungwitz et al., 2012 |
| OrxA (mice) | iBLA | 0.0001488 nmol (0.53 ng/0.5 μl) | ↑ Immobility in FST ↓ Social interaction in U-field test |
Kim et al., 2015 |
| OrxA (hamster) | iCeA | 0.02 nmol (20 nM) | ↑ Anxious and depressive behavior (LDT & EPM but not mentioned in review) | Avolio et al., 2011 |
| OrxA (rats) | i-pPVT | 28.08 nmol (0.1mg/250 nl) | ↑ Anxious behavior in EPM | Heydendael et al., 2011 |
| OrxA (rats) | iVP | 500 nmol (1 μM) | ↓ Anhedonia (Sucrose Preference) and behavioral despair (FST) after LV-shOrxlR knockdown | Ji et al., 2018 |
| OrxB | ||||
| OrxB (rats) | icv | 10 nmol | ↑ Locomotion, face-washing, grooming, wet-dog shaking | Matsuzaki et al., 2002 |
| OrxB (hamster) | iCeA | 0.06 nmol (60 nM) | ↑ Anxious and depressive behavior (LDT & EPM but not mentioned in review) | Avolio et al., 2011 |
| Orx1 antagonist | ||||
| SB-334867 (mice) | ip | 782.9 nmol (10 mg.kg) | ↓ Behavioral despair in FST & TST | Scott et al., 2011 |
| SB-334867 (mice) | ip | 234.9 nmol, 391.45 nmol, 782.9 nmol (3,5& 10 mg/kg) | ↓ Reaction to cued & contextual stimuli (freezing time to fear tests) | Flores et al., 2014 |
| SB-334867 (mice) | ip | 234.9–2,349 nmol1 (3–30 mg/kg) 782.9 nmol2 (10 mg/kg) | No general anxiety impact in EPM |
Rodgers et al, 20131 Scott et al., 20112 Staples & Cornish 20142 |
| SB-334867 (mice) | ip | 391.45 nmol & 782.9 nmol (5 & 10 mg/kg) | ↓ Anxiety induced by acute nicotine administration in EPM | Plaza-Zabala et al. 2010 |
| SB-334867 (rats) | ip | 1,879 nmol (20 mg/kg) | ↓ Hyperactivity in prenatal pups exposed to alcohol | Stettner et al., 2011 |
| SB-334867 (mice) | ip | 2,350 nmol (30 mg/kg) | ↓ Anxiety in OF induced by hypercapnic air | Johnson et al., 2012c |
| SB-334867 (rats) | ip | 30,530 nmol (30 mg/kg) | ↓ Freezing in Sprague-Dawley rats | Johnson et al., 2010 |
| SB-334867 (rats) | ip | 30,530 nmol (30 mg/kg) | ↓ Anxiety in SIP induced by hypercapnic air | Johnson et al., 2015 |
| SB-334867 (rats) | ip | 7,830 nmol (10 mg/kg) | ↓ Latency to approach novel & familiar predator odors | Staples & Cornish, 2014 |
| SB-334867 (ddY mice) | ip | 3,290 nmol (30 mg/kg) | ↓ Antidepressive action of icv OrxA inFST | Ito et al. 2008 |
| SB-334867 (rats) | i-pPVT | 313.2 nmol (0.1 mg/250 nl) | ↓ Anxious behavior in EPM | Heydenael et al. 2011 |
| SB-334867 (mice) | iBLA | 10 nmol | ↑ Contextually induced fear extinction | Flores et al. 2014 |
| GSK-1059865 (rats) | ip | 20,630 nmol (30 mg/kg) | ↓ Attenuate yohimbine induced stress fMRI | Gozzi et al. 2013 |
| Orx2 agonist | ||||
| Ala11-D-Leu15-OrxB (mice) | icv | 0.3 nmol | ↓ Anxious behaviors in stress-susceptible animals in the SAM | Staton et al. 2018 |
| Orx2 antagonist | ||||
| TCSOX229 (mice) | ip | 576.1 nmol & 864.1 nmol (10 & 15 mg/kg) | ↓ Freezing during contextual fear No effect w/ cued fear consolidation | Flores et al. 2014 |
| MK-1064 (mice) | icv | 0.3 nmol | ↑ Anxious behaviors in stress resilient animals in the SAM | Staton et al. 2018 |
| DORA | ||||
| DORA-12 (rats) | orally | 21,600 nmol (30 mg/kg) | ↓ Anxiety in SIP induced by hypercapnic air | Johnson et al. 2015 |
| Almorexant (rats) | orally | 14,600–146,000 nmol Dose dependent (30–300 mg/kg) | ↓ Fear potentiated startle in conditioned rats | Steiner et al 2012 |
| Almorexant (mice) | orally | 4,880 nmol per day (100 mg per day) | ↓ Anxious & depressive behaviors in UCMS model | Nollet et al. 2012 |
Drugs modifying orexin system and receptor activity used for preclinical and clinical treatments of anxious and depressive behaviors. Dosages presented as as converted to nmol based on either reported animal weights, or average weight for the development stage utilized in the study (and as published). A brief description of the drug’s effects on anxious and depressive behavior is included. Abbreviations: DORA = Dual Orexin Receptor Antagonist, EPM = Elevated Plus Maze, fMRI = functional Magnetic Resonance Imaging, FST = Forced Swim Test, iBLA = intra-Basolateral Amygdala, iBNST = intra-Bed Nucleus of the Stria Terminalis, iCeA= intra-Central Amygdala, icv = intracerebroventricular, ip = intraperitoneal, i-pPVT = intra-posterior Paraventricular Thalamus, iVP = intra-Ventral Pallidum, LDT = Light-Dark Test, OFT = Open Field Test, SAM = Stress-Alternatives Model, SIP = Social Interaction/Preference test, TST =Tail Suspension Test, UCMS = Unpredictable Chronic Mild Stress