State-dependent fear extinction with two benzodiazepine tranquilizers

Abstract

Four experiments with rats were run to investigate whether fear extinction conducted under the influence of a benzodiazepine transfers to the undrugged state. Fear was conditioned by pairing an experimental chamber with footshock and was assessed by observing freezing, a characteristic response of the rat to stimuli associated with shock. In Experiment 1, extinction of the chamber cues under chlordiazepoxide (librium) or diazepam (valium) was compared with extinction under a placebo; both drugs interfered with extinction in a dose-dependent manner as indicated by freezing during an undrugged test. Further results with chlordiazepoxide suggested that the effect depended on the drug's specific combination with extinction and that it occurred even though the extinction procedure otherwise eliminated fear completely (Experiment 2). Repeated preexposure to the drug, and the development of partial tolerance to its sedative effects, did not weaken the interference effect (Experiment 3). Other evidence suggested that the drug signaled or retrieved extinction instead of disrupting learning or consolidation (Experiment 4). The results are consistent with research suggesting that extinguished fear can be "renewed" if the exteroceptive contextual stimuli are changed after extinction. Extinction combined with either unique exteroceptive or interoceptive cues may be specific to its context.