Table 1.
Examples of effect of extinction facilitating and/or rescuing treatments in animal models of impaired extinction and human anxiety disordersa
| Agent class | Treatment | Animal studiesb | Human studies | |||
|---|---|---|---|---|---|---|
| FC | Model | Short-term extinction |
Extinction retrieval |
Efficacy as adjunct to exposure therapy |
||
| Adrenergic α2 R antagonist | Yohimbine | Cue | Genetic [20] | Nd | + | + Claustrophobia [106] |
| NMDAR agonist | DCS | Context | Stress [76] | Nd | + | + Acrophobia, social phobia |
| DCS | Cue | Genetic [20] | − | − | Panic disorder ([51,62,63]) | |
| DCS | Cue | Adolescent [107] | Post | + | −/(+) PTSD | |
| DCS | Cue* | Genetic [38] | Post | + | PTSD, +/− OCD ([51,56,57,62,63]) | |
| AMPAR agonist | PEPA | Cue | Genetic [38] | − | − | Nd |
| mGLUR7 agonist | AMN082 | Cue | Genetic [38] | + | + | Nd |
| FAAH inhibitor | AM3506 | Cue | Genetic [73] | + | + | Nd |
| SSRI | Fluoxetine | Cue | Genetic [54] | − | + | + PTSD [68], − social phobia [67] |
| HDAC inhibitor | MS-275 | Cue | Genetic [54] | − | − | Nd |
| Cue* | Genetic [54] | Post | + | Nd | ||
| Neurotrophic factors | BDNF | Cue | Stress [82] | + | ? | Nd |
| Neuropeptides | NPS | Cue | Stress [46] | + | ? | Nd |
| Multitarget (GABAergic, GC, GLUergic, HDAC inhibitor) |
ZnR | Cue | Genetic [54] | + | + | Nd |
| Multitarget (GABAeric, HDAC inhibitor) |
VPA | Cue | Genetic [54] | + | + | Nd |
| Other approaches | DBS | Cue | Genetic [54] | − | + | Nd |
a
DBS, accumbal deep brain stimulation; FC, fear conditioning; GC, glucocorticoid; GLU, glutamate; HDAC, histone deacetylase; Nd, not determined; post, given post extinction training (all other treatments given before or during extinction training); R, receptor; SSRI, selective serotonin reuptake inhibitor; VPA, valproic acid; ZnR, dietary zinc restriction.
b
+ effect, − no effect, +/− mixed results
*
weak fear conditioning.