Table 1
Summary of behavioral preclinical experiments using antagonists of OXR along with a brief description of some experimental details
| Antagonist | In vitro study (Cellular measurements) | In vivo (Proven action) | Procedure | Dose/Administration | Effect specificity | Author’s |
|---|---|---|---|---|---|---|
| SB-334867 | N/l | + | P female rat 2-bottle choice | 3, 10, or 30 mg/kg, i.p. | N/l | [4] |
| N/l | - | P female rat Operant progressive ratio | N/l | |||
| N/l | + | Male C57BL/6 mice Binge drinking | - | |||
| SB-334867 | + | + | All procedures 15%EtOH Male C57BL/6 mice Binge drinking 20%EtOH | 5 mg/kg, i.p. | N/l | [48] |
| SB-334867 | N/l | + | Male P rat Operant progressive ratio 10%EtOH | 3 μg VTA | + | [61] |
| SB-334867 | N/l | + | Female P rat Operant progressive ratio for EtOH->PSR ->Relapse ->SB administration>PSR ->Relapse 15%EtOH | 10 or 20 mg/kg, i.p. | N/l | [59] |
| SB-334867 | + | + | Male P rat Operant progressive ratio 10%EtOH | 5 or 10 mg/kg i.p. | + | [57] |
| SB-334867 | + | + | Male C57BL/6 mice 2-bottle choice 15%EtOH | 0.3, 1, 3 or 10 mg/kg i.p. | + | [49] |
| SB-334867 | + | mNAsh + mPFC + | Male C57BL/6 mice Binge drinking 15%EtOH | 3 μg mNAsh and mPFC | + | [50] |
| + | Male Long Evans rat Operant progressive ratio 20%EtOH | N/l | ||||
| SB-334867 | + | + | Male P rat Operant responding ratio 10%EtOH | 20 mg/kg, i.p. | + | [58] |
| GSK1059865 | + | + | Male C57BL/6 mice intermittent ethanol or air exposure in inhalation chambers 15%EtOH | 10, 25, 50 mg/kg i.p | + | [60] |
| SB-334867 | N/l | + | Male Wistar rat 2-bottle choice 10%EtOH | 3 ng, 6 ng NAcc | - | [44] |
| SB-334867 | N/l | + | Male Sprague Dawley rat 2-bottle choice 10%EtOH | 30 mg/kg, i.p. | + | [46] |
| SB-334867 | N/l | + | Male Sprague-Dawley rat Operant progressive ratio cue-induced reinstatement | 10, or 20 mg/kg i.p. | + | [47] |
| + | 20%EtOH | |||||
| SB-334867 | + | + | Male C57BL/6 mice Binge drinking 20%EtOH | 5 or 10 mg/kg, i.p. | - | [51] |
| SB-334867 | + | + | Male C57BL/6 mice Binge drinking 20%EtOH | 6.0 pg VTA and CeA | + | [55] |
| SB-334867 | - | + | Male Long-Evans rat Operant progressive ratio 10%EtOH | 5, 10, 15, 20 mg/kg, i.p. | + | [43] |
| SB-408124 | + | - | Male DBA/2 mice CPP | 3, 10, 30 mg/kg, s.c. | N/l | [45] |
| - | Male Wistar rat Operant progressive ratio | |||||
| All procedures 8%EtOH | ||||||
| SB-334867 | + | - | Male DBA/2J mice CPP | 10, 15, 20, 30, 40 mg/kg, i.p. | N/l | [52] |
| 20%EtOH | ||||||
| LSN2424100 | N/l | - | P female rat 2-bottle choice | 10 or 30 mg/kg, i.p. | N/l | [4] |
| N/l | + | P female rat Operant progressive ratio | 3, 10, 30 mg/kg i.p | N/l | ||
| N/l | + | Male C57BL/6 mice Binge drinking | 5, 30, 60 mg/kg i.p | - | ||
| All procedures 15%EtOH | ||||||
| TCS-OX2-29 | + | aPVT + pPVT- | Male Long-Evans rat 2-bottle-choice 20%EtOH | 10 nmol aPVT, pPVT | aPVT + pPVT- | [42] |
| TCS-OX2-29 | + | NAcc + NAcsh - | Male P rats cue-induced reinstatement of ethanol-seeking | 100 μg or 300 μg NAcsh or NAcc | + | [56] |
| + | Operant responding ratio 10%EtOH | |||||
| TCS-OX2-29 | + | Male C57BL/6 mice 2-bottle choice 15%EtOH | 3 or 10 mg/kg i.p | N/l | [49] | |
| TCS-OX2-29 | + | Male C57BL/6 mice Binge drinking 15%EtOH | 3 μg mNAsh | N/l | [50] | |
| - | Operant progressive ratio 20%EtOH | N/l | ||||
| TCS-OX2-29 | + | Male C57BL/6 mice Binge drinking 20%EtOH | 5.0, or 7.5 μg VTA, CeA | - | [55] | |
| JNJ10397049 | + | - | Male DBA/2 mice CPP | 1, 3, and 10 mg/kg, s.c. | + | [45] |
| + | Male Wistar rat Operant progressive ratio | |||||
| All procedures 8%EtOH | ||||||
| Almorexant | N/l | + | P female rat 2-bottle choice | 60 or 100 mg/kg, i.p. | N/l | [4] |
| + | P female rat Operant progressive ratio | 10, 30, or 60 mg/kg, i.p. | N/l | |||
| + | Male C57BL/6 mice Binge drinking | 5, 50, or 100 mg/kg, i.p. | - | |||
| All procedures 15%EtOH | ||||||
| Almorexant | + | VTA + SN - | Male Long-Evans rat Operant progressive ratio 20%EtOH | 3, 10 and 15 mg/kg, i.p. VTA and SN | - | [62] |
[i] (+) - confirmed effect, (-) - no effect, N/l - not investigated.
Antagonists of OXR1 - SB-334867, SB-408124, GSK1059865; Antagonists of OXR2 - TCS-OX2-29, JNJ10397049, LSN2424100; Dual Antagonist-Almorexant.
aPVT - anterior Paraventricular nucleus of the Thalamus, CeA - Central nucleus of the Amygdala, CPP - conditioned place preference, EtOH - Ethanol, mNAsh - medial Nucleus Accumbens shell, mPFC - medial Prefronal Cortex, NAcc - core of the Nucleus Accumbens, NAcsh - Nucleus Accumbens shell, pPVT - posterior Paraventricular nucleus of the Thalamus, PSR - Pavlovian Spontaneous Recovery, SN - Substantia Nigra, VTA - Ventral Tegmental Area.