BACKGROUND: Benzodiazepines reduce the effectiveness of fear extinction in rodents and of exposure therapy in people suffering from anxiety disorders if given concomitantly with the behavioral treatment from its onset. The present experiments used rats to examine whether benzodiazepines had the same detrimental effect when given after some initial extinction had been conducted drug-free.
METHODS: Rats were trained to fear a context (Experiments 1 and 2) or discrete cue (Experiment 3) and were extinguished to the context or cue under a benzodiazepine (midazolam) or vehicle. Extinction occurred either continuously in one session, with the drug or vehicle administered prior to the onset, or divided into two sessions, with the drug or vehicle administered prior to the second session. Rats were then tested, drug-free, for fear of the context or CS.
RESULTS: Midazolam disrupted context and cue extinction when administered prior to the initial session but failed to disrupt extinction when given prior to the second session.
CONCLUSIONS: The results in an animal model confirm that the effectiveness of extinction can be reduced when combined with benzodiazepines. They also suggest that the effectiveness of extinction will not be reduced when combined with a benzodiazepine if the patient has undergone some initial extinction drug-free.