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bioRxiv · 10.64898/2025.11.29.691323

Beta-Blocking Pavlov's Bells: Propranolol Attenuates Compound Extinction in an Error-Dependent Manner

Brink, A. K.·Martini, C. E.·Corbit, L. H.
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Abstract

A significant limitation of extinction-based therapies is their failure to be expressed across time and different contexts. The re-emergence of the original behaviour provides evidence that extinction training does not erase the original learning but rather relies on new learning that suppresses the expression of the original behaviour. Thus, a strategy for reducing relapse phenomena is to enhance the inhibitory learning that occurs during extinction training so that extinction is more robust. One such strategy is compound extinction where a combination of previously reinforced stimuli are presented together for the first time during extinction training. This treatment has been shown to enhance extinction learning, evidenced by reduced future spontaneous recovery. However, the mechanisms are not fully understood. Experiment 1 assessed whether the compound extinction effect is the result of increased expectation of reward generated by the compound of stimuli that is then violated, driving further learning, or more simply, the novelty of the compound which reengages attention and thus promotes extinction without increasing prediction error. Experiment 2 tested whether the effects of the noradrenaline beta-receptor antagonist propranolol, shown elsewhere to reduce the compound extinction effect, relate to prediction error or novelty. We found that, when equating the novelty of the stimulus compound, larger prediction error resulted in better extinction evidenced as reduced spontaneous recovery. Further, we found that propranolol reduced this effect suggesting that prediction error rather than novelty is important for both the behavioural and pharmacological effects. Together our results point to behavioural and pharmacological strategies that can be used to improve the long-term expression of extinction. HighlightsO_LIIncreasing prediction error during extinction enhances extinction retention C_LIO_LIThis effect is not explained by stimulus novelty C_LIO_LIBlocking beta-noradrenergic signaling attenuates the compound stimulus effect C_LI

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Brink, A. K., Martini, C. E., Corbit, L. H.. 2025-12-02. Beta-Blocking Pavlov's Bells: Propranolol Attenuates Compound Extinction in an Error-Dependent Manner. https://doi.org/10.64898/2025.11.29.691323

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