Elsevier

Neuroscience Letters

Volume 371, Issues 2–3, 23 November 2004, Pages 91-96
Neuroscience Letters

Behavioral effects of metyrapone on Pavlovian extinction

https://doi.org/10.1016/j.neulet.2004.08.046Get rights and content

Abstract

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.

Section snippets

Acknowledgments

This work was supported in part by National Institutes of Health grant R01 NS37755 to F. Gonzalez-Lima. The authors thank J. Shumake, J. Wommack, and Y. Delville for technical assistance.

References (27)

Cited by (83)

  • Environmental certainty influences the neural systems regulating responses to threat and stress

    2021, Neuroscience and Biobehavioral Reviews
    Citation Excerpt :

    Indeed, systemic administration of metyrapone, as well as intra-amygdala infusion of mifepristone, a glucocorticoid receptor antagonist, disrupted extinction learning (Yang et al., 2006). In slight contrast, another study found that systemic administration of metyrapone did not impact extinction learning, though later increases in spontaneous recovery and renewal were observed, suggesting that blocking corticosterone synthesis disrupts extinction memory consolidation (Barrett and Gonzalez-Lima, 2004). These and further studies highlighted below, raise the interesting possibility that endogenous glucocorticoid activity scales with threat predictability, whereby a lack of glucocorticoids disrupts threat response regulation by impairing learning processes about the actual likelihood of threat, whereas elevated glucocorticoid levels lead to generalization of threat assignment.

View all citing articles on Scopus
View full text