Table 1. Procedural Characteristics and Key Findings of Learned Safety Studies in Humans and Rodents.
| Paradigm | Behavioral/physiological tests | Subject/strain | Key finding | Refs |
|---|---|---|---|---|
| Human | ||||
| Conditional discrimination | Fear-potentiated startle | Healthy volunteers | Safety signal reduces anticipatory anxiety to threat stimulus | Grillon et al (1994b) |
| PD patients | Deficient discriminative learning to learned safety and danger cues driven by enhanced startle potentiation to the learned safety cue | Lissek et al (2009) | ||
| PTSD and MDD patients | Absence of fear inhibition to safety cues | Jovanovic et al (2010) | ||
| Skin conductance | Healthy volunteers | Dissociation within the ventromedial PFC between a safe stimulus previously predicting danger and a ‘naive' safe stimulus | Schiller et al (2008) | |
| Explicit unpairing CS–US | Pupillary diameter | Healthy volunteers | Learned safety involves reduced amygdalar and heightened dorsolateral PFC neural activity | Pollak et al (2010b) |
| Rodent | ||||
| Explicit unpairing CS–US | Fear-potentiated startle | Sprague–Dawley rats | Neural dissociations between the processing of appetitive and safety signals exist | Josselyn et al (2005) |
| Summation and retardation (freezing) | Learned safety leads to a reduction in spine size on synapses of the LA | Ostroff et al (2010) | ||
| Summation and retardation test (freezing), Open field, place preference | C57BL/6J mice | Learned safety reduces learned and instinctive fear, as well as positive affective responses | Rogan and LeDoux (1995) | |
| Summation and retardation test (freezing), FST, SPT | C57BL/6N mice | Learned safety acts as a behavioral antidepressant | Pollak et al (2008) | |
| Summation and retardation (freezing) | C57BL/6J, 129S1/SvImJ (S1) mice | S1 mice exhibit deficiencies in safety learning | Ostroff et al (2010) | |
| Inescapable shock (off-set pairing) | Social exploration | Sprague–Dawley rats | The sensory insula has a critical role in learned safety | Christianson et al (2008) |
| Safety signal-mediated reduction in neural fear responses during uncontrollable stressors involves the sensory insular cortex and BNST | Christianson et al (2011) | |||
| Active avoidance | Summation and retardation test (suppression of licking) | Wistar rats | Safety signal behaves as a conditioned inhibitor after long avoidance procedure | Cándido et al (2004) |
| Infant odor–shock pairing | FST, SPT | Long–Evans rats | An odor, which acquired characteristics of the maternal odor, serves as safety signal to revert depressive-like behavior and amygdala activity in adulthood, even when paired with shock infancy | Sevelinges et al (2011) |
Abbreviations: BNST, bed nucleus stria terminalis; FST, forced-swim test; LA, lateral amygdala; MDD, major depressive disorder; PFC, prefrontal cortex; PD, panic disorder; PTSD, post-traumatic stress disorder; SPT, sucrose preference test.