Behavioral effects of metyrapone on Pavlovian extinction

This is the first study of the action of metyrapone on Pavlovian extinction. Pavlovian acquisition memory can be impaired when 50 mg/kg metyrapone, a corticosterone synthesis inhibitor, is injected 90 min before training. It was hypothesized that the same treatment given before extinction may also impair Pavlovian extinction memory, and thereby facilitate recovery of the extinguished behavior. This study examined the behavioral effects of 50 mg/kg metyrapone on the extinction of conditioned freezing following Pavlovian conditioning of tone (CS) and footshock (US). On days 1-2, mice were habituated to the training context. On days 4-5, mice received 4 tone-shock pairings per day. On day 6, metyrapone or saline was injected s.c. 90 min before an extinction session with 60 tone presentations. Probe sessions with 4 tones were conducted in the extinction context on day 7 and in the acquisition context on day 9. Metyrapone treatment did not affect performance during extinction or pre-CS freezing behavior. But metyrapone-treated animals showed greater conditioned freezing when tested with the tone the day after extinction in the extinction context (spontaneous recovery) and 3 days after extinction in the acquisition context (renewal effect). It was concluded that 50 mg/kg metyrapone did not affect extinction performance, but it effectively facilitated the subsequent recovery of the extinguished behavior. This effect may be explained by an impairment of the consolidation of the Pavlovian extinction memory. This interpretation is consistent with previous studies showing that metyrapone may interfere with memory consolidation for a variety of learned responses.