Initial evidence for pharmacological modulation of observational threat learning by the GABAergic, but not the noradrenergic system in humans

Threat responses are often shaped by social information, such as observation of aversive outcomes for others. Yet, the neurochemistry regulating observational learning of threats is largely unknown. Here, we examined the impact of the GABAergic and noradrenergic system, which are central in regulating threat learning from first-hand experiences, on observational threat learning in humans. To this end, 61 participants received either 1 mg Lorazepam (enhancing GABAergic signalling N = 18), 20 mg Yohimbine (enhancing Noradrenergic transmission, N = 16), Placebo (double blind and randomized control for Lorazepam and Yohimbine, N = 12) or no treatment (N = 15) prior to observational threat conditioning. Participants acquired conditioned threat responses by observation of another individual who is presented with a conditioned stimulus (CS) and an aversive unconditioned stimulus (US). Participants' threat responses were tested by direct exposure to the CSs immediately after learning, as well as two days later (drug free). Our results indicate decreased fear ratings to socially acquired CSs by enhanced GABAergic transmission as compared to the control group (placebo and no treatment) during the immediate test. We could not provide evidence for noradrenergic modulation of socially acquired threat responses. Further, we found no differences in psychophysiological responses (Skin conductance responses) or long-term persistence of conditioned responses. Our results provide initial evidence for an impact of the GABAergic system on social acquisition of threats.