Table 3.
Pharmacological interventions in the fear-potentiated startle test
| Article | Drug | Species, strain | Dose (mg/kg) | Route, ITI (min) | Group size (*) | Reported effective dose (mg/kg); Direction of effect; ANOVA effect |
|||
|---|---|---|---|---|---|---|---|---|---|
| Non-cued startle | Cued startle | Difference score | % FPS | ||||||
| GABA-ergic system | |||||||||
| Benzodiazepines | |||||||||
| (Hijzen et al. 1995) | Alprazolam | Rat, Wi | 1, 2, 3 | IP, 30 | 12 | = |
NR; ↓; cue × dose |
NR | NR |
| (Jenck et al. 2000) | Alprazolam | Rat, Wi | 0.32, 1, 3.2 | IP, 30 | 16 | 1, 3.2; ↓ | 1, 3.2; ↓ | NR | NR |
| (Steiner et al. 2011) | Alprazolam | Rat, F344 | 0.3, 1. 3 | PO, NR | 16 | 1, 3; ↓ | 0.3, 1, 3; ↓ | 0.3, 1, 3; ↓ | 1, 3; ↓ |
| (Bill et al. 1992) | Chlordiazepoxide | Rat, LH | 5 | SC, 30 | 10 | 5; ↓ | 5; ↓ | NR | NR |
| (Guscott et al. 2000) | Chlordiazepoxide | Rat, SDR | 0.3. 1, 3, 10 | IP, 20 | 10 | 1, 3, 10; ↓ | 1, 3, 10; ↓ | 3, 10; ↓ | NR |
| (Guscott et al. 2000) | Chlordiazepoxide | Rat, SDR | 0.3, 1, 3, 10 | IP, 30 | 12 | 10; ↓ | 10; ↓ | 10; ↓ | NR |
| (Hijzen et al. 1995) | Chlordiazepoxide | Rat, Wi | 2.5, 5, 10 | IP, 20 | 12 | = |
NR; ↓; cue × dose |
NR | NR |
| (Joordens et al. 1996) | Chlordiazepoxide | Rat, Wi | 2.5, 5, 10 | IP, 20 | 8 | = |
NR; ↓; cue × dose |
NR | NR |
| (Joordens et al. 1996) | Chlordiazepoxide | Rat, Wi | 2.5, 5, 10 | IP, 20 | 12 | = |
NR; ↓; cue × dose |
NR | NR |
| (Joordens et al. 1997) | Chlordiazepoxide | Rat, Wi | 3.2, 10, 32 | SC, 20 | 8 | = |
NR; ↓; cue × dose |
NR | NR |
| (Risbrough et al. 2003) | Chlordiazepoxide | Mouse, DBA/1 J | 10 | IP, 30 | 6 | = |
NR; data shown |
NR | 10; ↓ |
| (Vale & Green 1996) | Chlordiazepoxide | Rat, HL | 2.5, 5 | IP, 30 | 10 | = | 2.5, 5; ↓ | NR | NR |
| (Varty et al. 2008) | Chlordiazepoxide | Rat, Wi | 1, 6, 10 | IP, 30 | 12–14 | = | NR | NR | 10; ↓ |
| (Zhao et al. 2018a) | Chlordiazepoxide | Rat, Wi | 2.5, 5, 10 | IP, 20 | 24 | NR; ↓ |
NR; ↓; cue × dose |
10; ↓ | NR |
| (Zhao et al. 2018a) | Chlordiazepoxide | Rat, Wi | 2.5, 5, 10 | IP, 20 | 54 | 2.5, 5, 10 ↓ | 2.5, 5, 10 ↓ | NR | 10; ↓ |
| Anthony & Nevins 1993) | Diazepam | Rat, SDR | 1 | IP, 30 | 8 | = |
NR; data shown |
1; ↓ | NR |
| (Brodkin et al. 2002) | Diazepam | Rat, Wi | 0.3, 1, 3 | SC, 30 | 8 | = | 3; ↓ | NR | NR |
| (Busse et al. 2004) | Diazepam | Rat, Wi | 0.3, 1, 3 | SC, 30 | 8 | = | 3; ↓ | NR | NR |
| (Collado et al. 2002) | Diazepam | NR | 0.6 | IP, NR | 8 | NR | NR | NR | NR |
| (Collado et al. 2004) | Diazepam | Rat, SDR | 0.6 | IP, NR | NR | NR | NR | 0.6; ↓ | NR |
| (Davis 1979) | Diazepam | Rat, SDR | 0.31, 0.62, 1.25, 2.5 | IP, 10 | 12 | = |
NR; data shown |
NR | 0.31, 0.62, 1.25, 2.5; ↓ |
| (Gacsályi et al. 2017) | Diazepam | Rat, SDR | 3 | IP, 30 | 8–14 | NR | NR | 3, ↓ | NR |
| (Helton et al. 1998) | Diazepam | Rat, LE | 0.03, 0.1, 0.3. 1 | IP, 30 | 8 | NR | NR | 0.1, 0.3, 1; ↓ | NR |
| (Johnson et al. 2003) | Diazepam | NR | 0.6 | IP, NR | NR | NR | NR | 0.6; ↓ | NR |
| (Johnson et al. 2005) | Diazepam | Rat, SDR | 0.6 | IP, NR | NR | NR | NR | 0.6; ↓ | NR |
| (Johnson et al. 2005) | Diazepam | Rat, SDR | 0.6 | IP, NR | NR | NR | NR | 0.6; ↓ | NR |
| (Joordens et al. 1997) | Diazepam | Rat, Wi | 1, 3.2, 10 | SC, 30 | 8*2 external control | = |
NR; ↓; cue × dose |
NR | NR |
| (Martin et al. 2002) | Diazepam | Rat, RORO | 0.3, 1, 3 | IP. 30 | 12 | 1; ↓ | 0.3, 1, 3; ↓ | 0.3, 1, 3; ↓ | NR |
| (Nevins & Anthony 1994) | Diazepam | Rat, SDR | 0.32, 1, 1.78, 3.2 | IP. 30 | 8 | = |
NR; data shown |
1, 1.78, 3.2; ↓ | NR |
| (Nevins & Anthony 1994) | Diazepam | Rat, SDR | 0.31, 1, 1.78. 3.2 | IP, 30 | 8 | = |
NR; data shown |
1, 1.78, 3.2; ↓ | NR |
| (Pietraszek et al. 2005) | Diazepam | Rat, SDR | 0.5, 1, 2 | IP, 30 | 14 | NR |
NR; data shown |
2; ↓ | NR |
| (Risbrough et al. 2003) | Diazepam | Mouse, DBA/1 J | 1, 3, 6 | IP, 30 | 9 to 15 | = | 6; ↓ | NR | 3, 6; ↓ |
| (Rorick-Kehn et al. 2007) | Diazepam | Rat, SDR | 0.6 | PO, 30 | 8 | NR | NR | 0.6; ↓ | NR |
| (Schulz et al. 2001) | Diazepam | Rat, SDR | 1.25 | IP, 30 | 10 | NR | NR | NR | 1.25; ↓ |
| (Steiner et al. 2012) | Diazepam | Rat, F344 | 1, 3, 10 | PO, 30 | 12 | 10; ↓ | 3, 10; ↓ | NR | NR |
| (Tizzano et al. 2002) | Diazepam | Rat, SDR | 0.3, 0.6, 1 | IP, 30 | 8 | = |
NR; data shown |
0.6, 1; ↓ | NR |
| (Tizzano et al. 2002) | Diazepam | Rat, SDR | 0.6 | IP, 30 | 8 | = |
NR; data shown |
0.6; ↓ | NR |
| (Tizzano et al. 2002) | Diazepam | Rat, SDR | 0.6 | IP, 30 | 8 | = |
NR; data shown |
0.6; ↓ | NR |
| (Zhang et al. 2016) | Diazepam | Rat, SDR | 2 | SC, 10 | 10 | NR | NR | NR | NR |
| (Zhao et al. 2018b) | Diazepam | Rat, Wi | 0.3, 1, 3 | IP, 30 | 24 | NR; ↓, main effect | No cue × dose | NR | NR |
| (Davis 1979) | Flurazepam | Rat, SDR | 2.5, 10, 20 | IP, 10 | 8 | = | NR; ↓ | NR | NR; ↓ |
| (Hijzen & Slangen 1989) | Midazolam | Rat, Wi | 0, 0.5, 1, 2 | IP, 10 | 12 | NR; ↓, main effect | No cue × dose | NR | NR |
| (Joordens et al. 1996) Utrecht | Oxazepam | Rat, Wi | 1, 3, 10 | PO, 60 | 12 | NR; ↓, main effect | No cue × dose | NR | NR |
| (Joordens et al. 1996) Oss | Oxazepam | Rat, Wi | 1, 3, 10 | PO, 60 | 12 | NR; ↓ |
NR; ↓; cue × dose |
NR | NR |
| Barbiturates | |||||||||
| (Chi 1965) | Amobarbital | Rat, SDR | 10, 20, 40 | IP, 10 | 10 | = | 10, 20, 40; ↓ | NR | NR |
| GABAA receptor agonists | |||||||||
| (Hijzen et al. 1995) | Alcohol | Rat, Wi | 500, 1000, 2000 | IP, 30 | 12 | = | = | NR | NR |
| GABAA receptor partial agonists | |||||||||
| (Guscott et al. 2000) | Bretazenil | Rat, SDR | 0.1, 0.3, 1, 3 | PO, 30 | 10–12 | 1; ↓ | 1, 3; ↓ | 1, 3; ↓ | NR |
| (Guscott et al. 2000) | Bretazenil | Rat, SDR | 0.1, 0.3, 1, 3 | PO, 30 | 10–12 | = | 1; ↓ | 1; ↓ | NR |
| (Guscott et al. 2000) | FG 8205 | Rat, SDR | 0.3, 1, 3, 10 | IP, 30 | 11 | 1, 3, 10; ↓ | 1, 3, 10; ↓ | 3, 10; ↓ | NR |
| (Guscott et al. 2000) | FG 8205 | Rat, SDR | 0.3, 1, 3, 10 | IP, 30 | 10–12 | = | 3, 10; ↓ | 3, 10; ↓ | NR |
| GABAA receptor α1 subunit agonist | |||||||||
| (Zhao et al. 2018b) | Zolpidem | Rat, Wi | 1, 3, 10 | IP, 15 | 24 | 3, 10; ↓ | 10; ↓ | 3; ↓ | NR |
| GABAA receptor α2,3 subunit agonist | |||||||||
| (Atack et al. 2006) | TPA023 | Rat, SDR | 0.3, 1, 3 | PO, 30 | 15 | = | 1, 3; ↓ | 1, 3; ↓ | NR |
| (Atack et al. 2011) | TPA023B | Rat, SDR | 0.1, 0.3, 1 | PO, 45 | 10 | = | 1; ↓ | 0.3, 1; ↓ | NR |
| GABAA receptor α5 subunit antagonist | |||||||||
| (Gacsályi et al. 2017) | S44819 | Rat, SDR | 1, 3, 10 | IP, 30 | 8–14 | = | NR | 1, 3; ↓ | NR |
| GABAA inverse receptor agonists | |||||||||
| (Risbrough & Geyer 2005) | FG-7142 | Mouse, DBA/1 J | 1, 3, 10, 20 | IP, 5 | 8 to 12 | = | 20; ↓ | NR | 10, 20; ↓ |
| (Risbrough & Geyer 2005) | FG-7142 | Mouse, 129/SvEv | 1, 3, 10, 20 | IP, 5 | 8 to 12 | = | = | NR | 3; ↓ |
| (Hijzen & Slangen 1989) | Lindane | Rat, Wi | 7.5, 15, 30 | PO, 180 | NR | NR; ↑; main effect | No cue × dose | NR | NR |
| (Bijlsma et al. 2010) | Pentylene tetrazole | Rat, Wi | 3, 10, 30 | IP, 10 | 9 | NR; ↓; main effect | No cue × dose | NR | = |
| (Hijzen & Slangen 1989) | DMCM | Rat, Wi | 0, 0.1, 0.2, 0.4 | IP, 6 | NR | NR; ↑; main effect | No cue × dose | NR | NR |
| GABAA receptor antagonist | |||||||||
| (Davis et al. 1988) |
Flumazenil aka Ro 15–1788 |
Rat, SDR | 2 | NR, NR | 5 | NR | NR | NR | NR |
| (Tizzano et al. 2002) | Flumazenil | Rat, SDR | 2 | IP, 60 | 8 | NR | NR | = | NR |
| GABAB receptor positive allosteric modulator | |||||||||
| (Li et al. 2015) | BHF177 | Rat, Wi | 20, 40 | PO, 60 | 15–16 | = | = | NR | = |
| Serotonergic system | |||||||||
| 5-HT1A receptor partial agonists (azapirones) | |||||||||
| (Brodkin et al. 2002) | Buspirone | Rat, Wi | 0.3, 1, 3 | IP, 30 | 8 | = | = | NR | NR |
| (Davis et al. 1988) | Buspirone | Rat, SDR | 5 | SC, 0 | 5 | NR | NR; ↓; cue x dose | NR | NR |
| (Li et al. 2015) | Buspirone | Rat, Wi | 1, 3 | SC, 10 | 12 | = | 3; ↓ | NR | 3; ↓ |
| (Mansbach & Geyer 1988) | Buspirone | Rat, SDR | 1.25, 2.5, 5 | SC, 10 | 10 | 1.25, 5 ↑ | = | 2.5, 5.0; ↓ | 2.5, 5.0; ↓ |
| (Nevins & Anthony 1994) | Buspirone | Rat, SDR | 0.56, 1, 3.2, 5.6 | IP, 30 | 8 | = | NR; data shown | 1, 3.2, 5.6; ↓ | NR |
| (Nevins & Anthony 1994) | Buspirone | Rat, SDR | 0.56, 1, 3.2, 5.6 | IP, 30 | 8 | = | NR; data shown | 1, 3.2, 5.6; ↓ | NR |
| (Risbrough et al. 2003) | Buspirone | Mouse, DBA/1 J | 2.5, 5, 10 | SC, 30 | 9 to 11 | = | = | NR | 5, 10; ↓ |
| (Steiner et al. 2012) | Buspirone | Rat, F344 | 10, 30, 100 | PO, 30 | 12 | 10, 30, 100; ↑ | 100; ↓ | NR | NR |
| (Mansbach & Geyer 1988) | Gepirone | Rat, SDR | 3, 10 | IP, 10 | 7 to 8 | = | = | = | 10; ↓ |
| (Davis et al. 1988) | Ipsapirone | Rat, SDR | 10, 20, 40 | IP, 0 | 5 | 40; ↓ | 40; ↓ | 40; ↓ | NR |
| (Mansbach & Geyer 1988) | Ipsapirone | Rat, SDR | 1, 3, 5.6, 10 | SC, 10 | 10 | = | = | 5.6; ↓ | 3.0, 5.6; ↓ |
| 5-HT1A biased receptor agonists | |||||||||
| (Zhao et al. 2019) | F13714 | Rat, Wi | 0.01, 0.04, 0.16 | IP, 60 | 12 | 0.04, 0.16; ↓ | 0.16; ↓ | NR | NR |
| (Zhao et al. 2019) | F15599 | Rat, Wi | 0.01, 0.04, 0.16 | IP, 60 | 12 | = | = | NR | NR |
| 5-HT1A receptor agonists | |||||||||
| (Davis et al. 1988) | 8-OH-DPAT | Rat, SDR | 2.5, 5, 10 | IP, 0 | 5 (10) | NR | NR | no dose effect | NR |
| (Joordens et al. 1998) | 8-OH-DPAT | Rat, Wi | 0.03, 0.1, 0.3 | SC, 10 | 12 | = | 0.3; ↓ | NR | NR |
| (Joordens et al. 1998) | 8-OH-DPAT | Rat, Wi | 0.3 | SC, 10 | 35 (36) | NR | NR | 0.3; ↓ | NR |
| (Mansbach & Geyer 1988) | 8-OH-DPAT | Rat, SDR | 0.125, 0.5 | SC, 10 | 10 | = | = | 0.125, 0.25; ↓ | 0.125, 0.25; ↓ |
| (Zhao et al. 2019) | R( +)-8-OH-DPAT | Rat, Wi | 0.03, 0.1, 0.3 | SC, 10 | 12 | 0.03, 0.1, 0.3; ↓ | 0.03, 0.1, 0.3; ↓ | NR | NR |
| (Joordens et al. 1998) | Flesinoxan | Rat, Wi | 10 | PO, 60 | 35 (36) | NR | NR | 10; ↓ | NR |
| (Joordens et al. 1996) Utrecht | Flesinoxan | Rat, Wi | 1, 3, 10 | PO, 60 | 12 | = | NR; ↓; cue x dose | NR | NR |
| (Joordens et al. 1996) Oss | Flesinoxan | Rat, Wi | 1, 3, 10 | PO, 60 | 12 | dose NR; ↓ | NR; ↓; cue x dose | NR | NR |
| 5-HT1A receptor antagonists | |||||||||
| (Joordens et al. 1998) | DU125,530 | Rat, Wi | 1, 3, 10 | SC, 30 | 12 | = | 1, 3, 10; ↓ | NR | NR |
| (Joordens et al. 1998) | Pindolol | Rat, Wi | 3, 10, 30 | SC, 30 | 11 | = | 10, 30; ↓ | NR | NR |
| (Joordens et al. 1998) | WAY100,635 | Rat, Wi | 0.1, 0.3, 1 | SC, 30 | 12 | = | 1; ↓ | NR | NR |
| (Risbrough & Geyer 2005) | WAY100,635 | Mouse, DBA/1 J | 0.3 | IP, 10 | 8 to 12 | = | = | NR | NR |
| (Zhao et al. 2019) | WAY100,635 | Rat, Wi | 0.1, 0.3, 1 | SC, 30 | 12 | 0.1, 0.3, 1; ↓; main effect | no cue x dose | NR | NR |
| 5-HT2c receptor agonists | |||||||||
| (Bijlsma et al. 2010) | m-CPP | Rat, Wi | 0.5, 1, 2 | IP, 25 | 8 | NR; ↓, main effect | no cue x dose | NR | 2; ↑ |
| (Mansbach & Geyer 1988) | m-CPP | Rat, SDR | 0.25, 1 | SC, 10 | 10 | 1; ↓ | 1; ↓ | = | = |
| (Risbrough & Geyer 2005) | m-CPP | Mouse, DBA/1 J | 0.3, 1, 3 | SC, 15 | 8 to 12 | 3; ↑ | 3; ↑ | NR | = |
| 5-HT2a, 2c receptor antagonists | |||||||||
| (Davis et al. 1988) | Cinanserin | Rat, SDR | 10 | IP, NR | 5 | NR | NR | NR | NR |
| (Mansbach & Geyer 1988) | Methysergide | Rat, SDR | 0.3, 1, 3, 10 | SC, 10 | 7 to 8 | 1; ↑ | = | = | = |
| (Davis et al. 1988) | Cyproheptadine | Rat, SDR | 5 | NR, NR | 5 | NR | NR | NR | NR |
| (Martin et al. 2002) | SB-242084 | Rat, RORO | 0.1, 0.3, 1 | IP, 30 | 12 | = | = | = | NR |
| 5-HT3 receptor antagonists | |||||||||
| (Nevins & Anthony 1994) | (R)-Zacopride | Rat, SDR | 0.001, 0.01, 0.1, 1 | IP, 45 | 8 | = | NR; data shown | 1; ↓ | NR |
| (Nevins & Anthony 1994) | (R)-Zacopride | Rat, SDR | 0.001, 0.01, 0.1, 1 | IP, 45 | 8 | = | NR; data shown | 0.01, 0.1, 1; ↓ | NR |
| (Nevins & Anthony 1994) | Granisetron | Rat, SDR | 0.001, 0.01, 0.1, 1 | IP, 45 | 8 | = | NR; data shown | = | NR |
| (Nevins & Anthony 1994) | Granisetron | Rat, SDR | 0.001,0,01, 0,1, 1 | IP, 45 | 8 | = | NR; data shown | 0.01, 0.1, 1; ↓ | NR |
| (Nevins & Anthony 1994) | Ondansetron | Rat, SDR | 0.001, 0.01, 0.1, 1 | IP, 45 | 8 | = | NR; data shown | = | NR |
| (Nevins & Anthony 1994) | Ondansetron | Rat, SDR | 0.001, 0.01, 0.1, 1 | IP, 45 | 8 | = | NR; data shown | 0.001, 0.01, 0.1, 1; ↓ | NR |
| (Nevins & Anthony 1994) | Ondansetron | Rat, SDR | 0.1 | IP, 45 | 8 | = | NR; data shown | 0.1; ↓ | NR |
| (Nevins & Anthony 1994) | Ondansetron | Rat, SDR | 0.1 | IP, 45 | 8 | = | NR; data shown | = | NR |
| (Nevins & Anthony 1994) | Ondansetron | Rat, SDR | 0.1 | IP, 45 | 8 | = | NR; data shown | 0.1; ↓ | NR |
| (Nevins & Anthony 1994) | Ondansetron | Rat, SDR | 0.1 | IP, 45 | 8 | = | NR; data shown | 0.1; ↓ | NR |
| Bill et al. 1992 | WAY100289 | Rat, LH | 0.003, 0.03, 0.3 | SC, 30 | 10 | NR | NR | NR | NR |
| 5-HT re-uptake inhibitors (SSRIs) | |||||||||
| (Steiner et al. 2012) | Fluoxetine | Rat, F344 | 3, 10, 30 | PO, 45 | 12 | = | = | NR | NR |
| (Joordens et al. 1996) | Fluvoxamine | Rat, Wi | 5, 10, 20 | PO, 60 | 12 | = | = | NR | NR |
| (Joordens et al. 1996) | Fluvoxamine | Rat, Wi | 5, 10, 20 | PO, 60 | 12 | = | = | NR | NR |
| (Steiner et al. 2012) | Sertraline | Rat, F344 | 10, 30, 100 | PO, 60 | 12 | 30, 100; ↑ | 30, 100; ↑ | NR | NR |
| TCAs | |||||||||
| (Hijzen et al. 1995) | Amitriptyline | Rat, Wi | 2.5, 5, 10 | IP, 60 | 12 | = | = | NR | NR |
| Cassella 1985 | Imipramine | Rat, SDR | 5, 10 | IP, 0 | 10 | = | = | = | NR |
| (Nevins & Anthony 1994) | Imipramine | Rat, SDR | 5, 10 | IP, NR | 8 | = | NR; data shown | = | NR |
| 5-HT releaser | |||||||||
| (Davis et al. 1988) | p-Chloro-amphetamine | Rat, SDR | 5 | IP, 15 | 5 | NR | NR | NR | NR |
| Glutamatergic system | |||||||||
| mGluR1antagonists | |||||||||
| (Pietraszek et al. 2005) | EMQMCM | Rat, SDR | 1.25, 2.5, 5 | IP, 30 | 16 | = | NR; data shown | 5; ↓ | NR |
| mGLuR5 antagonists | |||||||||
| (Carcache et al. 2011) | 15i | NR | 0.3, 1, 3 | PO, 60 | 10 | NR | NR;data shown | 1, 3; ↓ | NR |
| (Brodkin et al. 2002) | MPEP | Rat, Wi | 3, 10, 30 | IP, 60 | 8 | = | 10, 30; ↓ | NR | NR |
| (Schulz et al. 2001) | MPEP | Rat, SDR | 0.3, 3, 10 | PO, 60 | NR | = | 30; ↓ | 30; ↓ | NR |
| (Cosford et al. 2003) | MPEP | NR | NR | IP, NR | 8 | NR | NR | NR | NR |
| Busse et al. 2004 | MTEP | Rat, Wi | 0.3, 1, 3 | IP, 60 | 8 | = | 1, 3; ↓ | NR | NR |
| (Pietraszek et al. 2005) | MTEP | Rat, SDR | 0.6, 1.25, 2.5, | IP, 30 | 14 | = | NR, data shown | 2.5, 5; ↓ | NR |
| (Cosford et al. 2003) | MTEP | NR | NR | IP, NR | 8 | NR | NR | NR | NR |
| (Roppe et al. 2004a) | 5-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-2,30-bipyridine (MTEP derivate | NR | NR | PO, 60 | NR | NR | NR | NR | NR |
| (Roppe et al. 2004b) | 3-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitrile (MTEP derivate) | Rat, Wi | NR | PO, 60 | 8 | NR | NR | NR | NR |
| mGluR2,3 agonists | |||||||||
| (Collado et al. 2004) | (2S,1'S,2'R,3'R)-2-(2¢-carboxy-3¢-hydroxymethylcyclopropyl) glycine (( +)-3) | Rat, SDR | 0.003, 0.04, 0.3, 3 µg/kg | , NR | NR | NR | NR | 0.3, 3 µg/kg; ↓ | NR |
| (Collado et al. 2002) | (2S,1'S,2'S,3'R)-2-(2¢-carboxy-3'-methylcyclopropyl) glycine | NR | NR | PO, NR | 8 | NR | NR | NR | NR |
| (Johnson et al. 2005) | APPES | Rat, SDR | 0.0001, 0.001, 0.01, 0.1 | SC, NR | NR | NR | NR | 0.1; ↓ | NR |
| (Helton et al. 1998) | (-)-LY366563 | Rat, LE | 1, 3, 10 | PO, 60 | 16 | = | NR | = | NR |
| (Helton et al. 1998) | ( +)-LY354740 | Rat, LE | 0.01, 0.03, 0.1, 1, 3, 10 | PO, 60 | 16 | = | NR | 0.1, 1, 3, 10; ↓ | NR |
| (Tizzano et al. 2002) | ( +)-LY354740 | Rat, SDR | 0.3 | IP, 30 | 8 | NR | NR | 0.3; ↓ | NR |
| (Tizzano et al. 2002) | ( +)-LY354740 | Rat, SDR | 0.003, 0.03, 0.3, 3 | IP, 30 | 8 | = | NR, data shown | 0.3, 3; ↓ | NR |
| (Tizzano et al. 2002) | ( +)-LY354740 | Rat, SDR | 0.3 | IP, 30 | 8 | = | NR, data shown | 0.3; ↓ | NR |
| (Rorick-Kehn et al. 2007) | LY404039 | Rat, SDR | 0.03, 0.3, 3, 30 µg/kg | PO, 30 | 8 | NR | NR | 3, 30 µg/kg; ↓ | NR |
| (Rorick-Kehn et al. 2007) | LY404039 | Rat, SDR | 30 µg/kg | PO, 30 | 8 | NR | NR | 30 µg/kg; ↓ | NR |
| (Johnson et al. 2003) | LY487379 | NR | 0.03, 0.3, 3 | IP, NR | NR | NR | NR | 3; ↓ | NR |
| (Johnson et al. 2005) | LY487379 (aka 4-MPPTS) | Rat, SDR | 0.001, 0.01, 0.1, 1 | SC, NR | NR | NR | NR | 1; ↓ | NR |
| mGluR2,3 antagonists | |||||||||
| (Tizzano et al. 2002) | LY341495 | Rat, SDR | 1 | SC, 60 | 8 | = | NR, data shown | = | NR |
| (Tizzano et al. 2002) | LY341495 | Rat, SDR | 1 | SC, 60 | 8 | = | NR, data shown | = | NR |
| (Rorick-Kehn et al. 2007) | LY341495 | Rat, SDR | 1 | SC, 60 | 8 | NR | NR | = | NR |
| (Johnson et al. 2003) | LY341495 | NR | 3 | SC, NR | NR | NR | NR | = | NR |
| GlyR partial agonists | |||||||||
| Anthony & Nevins 1993) | 1-aminocyclopropanecarboxylate | Rat, SDR | 10, 30, 100, 200 | IP, 15 | 8 | = | NR; data shown | 200; ↓ | NR |
| Anthony & Nevins 1993) | 1-aminocyclopropanecarboxylate | Rat, SDR | 200, 300, 400, 500 | IP, 15 | 8 | = | NR; data shown | 200, 300, 400, 500; ↓ | NR |
| Anthony & Nevins 1993) | ( +)-HA-966 | Rat, SDR | 1, 3, 10 | IP, 15 | 8 | = | NR; data shown | 10, 30; ↓ | NR |
| Anthony & Nevins 1993) | d-Cycloserine | Rat, SDR | 10, 30, 100, 300 | IP,15 | 8 | = | NR; data shown | 30, 100, 300; ↓ | NR |
| (Anthony & Nevins 1993) | d-Cycloserine | Rat, SDR | 10, 30, 100, 300 | IP,15 | 8 | = | NR; data shown | 30, 100, 300; ↓ | NR |
| (Walker et al. 2002) | d-Cycloserine | Rat, SDR | 15 | IP, 30 | 5 (6) | NR | NR | NR | = |
| GlyR antagonists | |||||||||
| (Anthony & Nevins 1993) | 7-chlorokynurenate | Rat, SDR | 10, 30, 100 | IP, 15 | 8 | = | NR; data shown | 30, 100; ↓ | NR |
| (Walker et al. 2002) | ( ±)-HA-966 | Rat, SDR | 6 | IP, 40 | 5 (6) | NR | NR | NR | = |
| GluN receptor antagonists | |||||||||
| Anthony & Nevins 1993) | 2-amino-7-phosphonoheptanote | Rat, SDR | 10, 30 | IP, 15 | 8 | = | NR; data shown | 10, 30; ↓ | NR |
| Anthony & Nevins 1993) | 3-(2-carboxypiperazin-4-yl)propyl 1-phosphonate (CPP) | Rat, SDR | 3 | IP, 15 | 8 | = | NR; data shown | 3; ↓ | NR |
| (Zhang et al. 2016) | Phencyclidine | Rat, SDR | 1.5 | IP, 10 | 10 | NR | NR | NR | NR |
| Noradrenergic system | |||||||||
| α1-adrenoreceptor antagonists | |||||||||
| (Davis 1979) | WB4101 | Rat, SDR | 1 | IP, 10 | 10 | = | NR | NR | = |
| α2-adrenoreceptor antagonists | |||||||||
| (Risbrough & Geyer 2005) | Atipamezole HCL | Mouse, DBA/1 J | 0.3, 1, 3 | SC, 30 | 8 to 12 | 3; ↑ | 3; ↑ | NR | = |
| (Davis 1979) | Piperoxane | Rat, SDR | 0.25, 1 | IP, 10 | 10 | = | 1; ↑ | NR | 1; ↑ |
| (Bijlsma et al. 2010) | Yohimbine | Rat, Wi | 0.25, 0.5, 1 | IP, 10 | 11 | = | 0.25, 1; ↑ | = | = |
| (Davis 1979) | Yohimbine | Rat, SDR | 0.125, 0.25 | IP, 10 | 10 | = | 0.25; ↑ | NR | 0,25; ↑ |
| (Davis et al. 1988) | Yohimbine | Rat, SDR | 5 | IP, NR | 5 | NR | NR | NR | NR |
| (Risbrough & Geyer 2005) | Yohimbine | Mouse, DBA/1 J | 0.1, 1, 10 | SC, 30 | 8 to 12 | = | NR; ↓ | NR | 10; ↓ |
| α2-adrenoreceptor agonists | |||||||||
| (Davis 1979) | Clonidine | Rat, SDR | NA | IP, 10 µg/kg | NR | NR; ↓ | NR; ↓ | NR | NR; ↓ |
| β1,2-adrenoreceptor antagonists | |||||||||
| (Davis 1979) | Propranolol | Rat, SDR | 20 | IP, 10 | 10 | = | NR | NR | = |
| Dopaminergic system | |||||||||
| D1 receptor agonists | |||||||||
| (de Oliveira et al. 2006) | SKF 38,393 | Rat, Wi | 5, 10 | IP, 10 | 20 | = | = | NR | NR |
| D1 receptor antagonists | |||||||||
| (de Oliveira et al. 2006) | SCH 23,390 | Rat, Wi | 0.05, 0.1 | IP, 30 | 20 | = | = | NR | NR |
| D2 receptor agonists | |||||||||
| (de Oliveira et al. 2006) | Quinpirole | Rat, Wi | 0.1, 0.25 | IP, 10 | 15 | = | 0.1, 0.25; ↓ | NR | NR |
| D2 receptor antagonists | |||||||||
| (Hijzen et al. 1995) | Haloperidol | Rat, Wi | 0.065, 0.125, 0.25 | IP, 30 | 12 | = | NR; ↓; cue x dose | NR | NR |
| Muthuraju 2014 | Haloperidol | Rat, Wi | 0.1, 0.5 | IP, 5 | 10–17 | = | 0.1, 0.5; ↓ | NR | NR |
| (Nevins & Anthony 1994) | Haloperidol | Rat, SDR | 0.1, 0.3 | IP, NR | 8 | = | NR; data shown | = | NR |
| (de Oliveira et al. 2006) | Sulpiride | Rat, Wi | 20, 40 | IP, 10 | 15 | = | = | NR | NR |
| Psychostimulants | |||||||||
| (Vale & Green 1996) | d-Amphetamine | Rat, LH | 0.5, 1 | IP, 30 | 11–12 | = | = | NR | NR |
| (Hijzen et al. 1995) | d-Amphetamine | Rat, Wi | 0.6, 1.2, 2.4 | IP, 15 | 12 | = | NR; ↓; cue x dose | NR | NR |
| Opioid system | |||||||||
| μ receptor partial agonists | |||||||||
| (Glover & Davis 2008) | Buprenorphine | Rat, SDR | 0.004, 0.0075, 0.015, 0.03, 0.25 | SC, 0 | 45 (NR) | = | NR; ↓ | 0.0075, 0.015, 0.03, 0.25; ↓ | NR |
| μ receptor agonists | |||||||||
| (Davis 1979) | Morphine | Rat, SDR | 0.63, 2.5, 10 | IP, 10 | 8 | = | NR; ↓ | NR | NR |
| (Davis 1979) | Morphine | Rat, SDR | 10 | IP, 10 | 8 | = | 10; ↓ | NR | NR |
| (Glover & Davis 2008) | Morphine | Rat, SDR | 0.03, 0.25, 0.63, 2.5, 10 | SC, 0 | 45 (NR) | = | NR; ↓ | 0.63, 2.5, 10; ↓ | NR |
| (Hijzen et al. 1995) | Fentanyl | Rat, Wi | 0.0025, 0.01, 0.04 | IP, 30 | 12 | = | = | NR | NR |
| μ receptor antagonists | |||||||||
| (Davis 1979) | Naloxone | Rat, SDR | 2 | IP, 20 | 8 | = | = | NR | NR |
| (Davis et al. 1988) | Naloxone | Rat, SDR | 5 | NR, NR | 5 | NR | NR | NR | NR |
| (Hijzen et al. 1995) | Naloxone | Rat, Wi | 2.5, 5, 10 | IP, 25 | 12 | = | = | NR | NR |
| (Glover & Davis 2008) | Naloxone | Rat, SDR | 0.5 | SC, 5 | NR | NR | NR | = | NR |
| Neuropeptides | |||||||||
| BB1,2 receptor antagonists | |||||||||
| (Merali et al. 2006) | PD176252 | Rat, NR | 5, 10 | IP, 20 | 9 | = | 5, 10; ↓ | NR | NR |
| Cholecystokinin system | |||||||||
| CCK2 receptor agonists | |||||||||
| (Hebb et al. 2003) | Boc CCK-4 | Mouse, CD1 | 5, 15 µg/kg | SC, 30 | 5 | = | 15; ↓ | NR | NR |
| CCK2 receptor antagonists | |||||||||
| (Josselyn et al. 1995) | L-365,260 | Rat, Wi | 0.1, 1, 10 | IP, 15 | 16 (11) | = | 1, 10; ↓ | NR | NR |
| CRF system | |||||||||
| CRF1 receptor antagonists | |||||||||
| (Bijlsma et al. 2015) | CP154,526 | Rat, Wi (wt) | 10 µg/kg | IP, 30 | 9–10 | NR; ↓; main effect | no cue x dose | NR | NR |
| (Chen et al. 1997) | CP-154,526 | Rat, SDR | 17.8 | PO, 60 | NR (12) | = | NR | 17.8; ↓ | NR |
| (Risbrough et al. 2009) | NBI-30775 | Mouse, C57BL/6 J | 20 | IP, 30 | 7–13 | NR | NR | NR | = |
| Ghrelin-R1a agonist | |||||||||
| (Toufexis et al. 2016) | Ghrelin | Rat, SDR male | 10 | SC, 20 | 16 | = | NR | NR | = |
| (Toufexis et al. 2016) | Ghrelin | Rat, SDR female | 10 | SC, 20 | 16 | = | NR | NR | = |
| NOP receptor agonists | |||||||||
| (Varty et al. 2008) | SCH 221,510 | Rat, Wi | 3, 6, 10 | PO, 120 | 12–14 | = | NR | NR | NR; ↓ |
| (Jenck et al. 2000) | Ro 64–6198 | Rat, Wi | 1, 3.2, 10 | IP, 30 | 16 | 3.2, 10; ↓ | 3.2, 10; ↓ | NR | NR |
| (Lu et al. 2011) | SCH 655,842 | Rat, Wi | 1, 3, 10 | PO, 60 | 12–15 | = | NR | NR | 3, 10; ↓ |
| NTS1 receptor agonists | |||||||||
| (Shilling & Feifel 2008) | PD149163 | Rat, SDR | 0.01, 0.1, 1.0 | SC, 20 | 7–10 | = | NR | NR | 1; ↓ |
| (Shilling & Feifel 2008) | PD149163 | Rat, SDR | 1 | SC, 20 | 16 | 1; ↓ | NR | NR | 1; ↓ |
| OX1,2 receptor antagonists | |||||||||
| (Steiner et al. 2012) | Almorexant | Rat, F344 | 30, 100, 300 | PO, 60 | 12 | 300; ↓ | 100, 300; ↓ | NR | NR |
| OX1 receptor antagonists | |||||||||
| (Steiner et al. 2013) | ACT-335827 | Rat, F344 | 30, 100, 300 | PO, 60 | 16 | = | 300; ↓ | NR | NR |
| OT receptor agonists | |||||||||
| (Ayers et al. 2011) | Oxytocin | Rat, SDR | 0.01, 0.1, 1.0 µg/kg | SC, 30 | 12 | 0.001, 0.1; ↓ | = | NR | = |
| (Ayers et al. 2016) | Oxytocin | Rat, SDR | 0.1 | SC, 30 | 55 (54) | NR; ↓; main effect | no cue x dose | NR | = |
| (Missig et al. 2010) | Oxytocin | Rat, SDR | 0.01, 0.1, 1 µg/kg | SC, 30 | 12 | NR; ↓; main effect | no cue x dose | NR | = |
| Secretin receptor agonists | |||||||||
| (Myers et al. 2004) | Secretin | Rat, SDR | 1, 3, 10, 30, 100 µg/kg | IP, 0 | 16 (8–12) | = | NR | 10; ↓ | = |
| Miscellaneous | |||||||||
| Cholinergic system | |||||||||
| nACh receptor agonists | |||||||||
| (Hijzen et al. 1995) | Nicotine | Rat, Wi | 0.4, 0.8, 1.6 | IP, 15 | 12 | = | = | NR | NR |
| (Vale & Green 1996) | Nicotine | Rat, LH | 0.05, 0.1, 0.4 | SC, 0 | 10–12 | = | = | NR | NR |
| (Vale & Green 1996) | Nicotine | Rat, LH | 0.1 | SC, 0 | 10 | = | = | NR | NR |
| Endocannabinoid system | |||||||||
| CB1 receptor antagonists | |||||||||
| (Chhatwal et al. 2005) | Rimonabant | Rat, SDR | 5 | IP, 60 | 8 | NR | NR | NR | = |
| Endocannabinoid reuptake inhibition | |||||||||
| (Chhatwal et al. 2005) | AM404 | Rat, SDR | 10 | IP, 60 | 8 | = | NR | NR | = |
| Glucocorticoid system | |||||||||
| MR/GR receptor agonists | |||||||||
| (de Oliveira et al. 2013) | Corticosterone | Rat, Wi | 3, 6 | IP, 0 | 6 (12) | = | = | NR | NR |
| Corticosterone synthesis blocker | |||||||||
| (de Oliveira et al. 2013) | Metyrapone | Rat, Wi | 30, 60 | IP, 20 | 6 (12) | = | = | NR | NR |
| Other | |||||||||
| Voltage dependent sodium channel blocker | |||||||||
| (Hijzen et al. 1995) | Carbamazepine | Rat, Wi | 5, 10, 20 | IP, 60 | 12 | = | = | NR | NR |
FPS fear potentiation, IP intraperitoneally, ITI inter-trial interval, LE Long Evans, NR not reported, PO per os, SC subcutaneously, SDR Sprague–Dawley rat, Wi Wistar, wt wild type, CRF corticotropin-releasing factor, GluN ionotropic glutamate receptor, GlyR glysine receptor, m-CPP m-chlorophenylpiperazine, mGlu metabotropic glutamate, MR/GR mineralocorticoid receptor/glucocorticoid receptor, nACh nicotinic acetylcholine, NOP nociceptin opioid peptide, NTS neurotensin, OT oxytocin, OX orexin, ↓ response reduced relative to vehicle control condition, ↑ response increased relative to vehicle control condition, cue × dose interaction effect in ANOVA
(*) group size of intervention group is given in brackets if the group size of the experimental group differed from that of the vehicle-control group