Limited efficacy of propranolol on the Limited efficacy of propranolol on the reconsolidation of fear memoriesreconsolidation of fear memories

Speaker :Chi-Yuan Chang

Advisor : Yn-ho Huang Ph.D.

Elizaveta V. Muravieva1 and Cristina M. Alberini1,2,31Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, USA; 2Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA

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Introduction Introduction

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RetrievalReconsolidationConsolidation

Consolidation Long-lasting memoryLabile state

McGaugh 2000

Nader et al. 2000, Sara 2000

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Retrieval

ReconsolidationConsolidation

Inhibition of protein and RNA synthesisBlockade of neurotransmitter and hormone receptors

Davis and Squire 1984; Izquierdo and Medina 1997; Kandel 2001

Interfering with the reconsolidation process provides an opportunity for disrupting memories that may contribute to the development of psychiatric disorders such as post-traumatic stress disorder (PTSD) or addiction.

(Dudai 2006; Diergaarde et al. 2008; Taylor et al. 2009)

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Particular attention has been given to blockers of stress hormones, including antagonists of glucocorticoid or B-adrenergic receptors.

We previously reported that the glucocorticoid receptor antagonist RU38486 persistently disrupts inhibitory avoidance (IA) memory retention if administered either in the amygdala or systemically immediately following retrieval.

Thus, we were interested in investigating the potential synergistic effect of blocking both glucocorticoid and B-adrenergic receptors.

Several studies from other laboratories have investigated the effect of the B-adrenergic receptor antagonist propranolol on fear memories, but reported conflicting conclusions.

(Tronel and Alberini 2007; Taubenfeld et al. 2008)

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AimAim

It remains to be established whether propranolol interferes with the reconsolidation of fear memories at large.

RetrievalReconsolidationConsolidation

Propranolol

Interfering with the reconsolidation process provides an opportunity for disrupting memories that may contribute to the development of psychiatric disorders such as post-traumatic stress disorder (PTSD) or addiction. (Dudai 2006; Diergaarde et al. 2008; Taylor et al. 2009)

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Materials and MethodsMaterials and Methods

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AnimalsAnimals

Long evans adult male rats Weight 250~350 g 12-h light-dark cycle Experiment 9 AM~6 PM

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http://whitelab.biology.dal.ca/ln/leah.html

Inhibitory avoidance (IA)

Training

Test Latency

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Freezing

FreezingTraining

Context test

Cue test

Fear conditioning (FC)

Context A Context A

Context A

Context B

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ResultsResults

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Question: Propranolol administrated systemically immediately

after retrieval has effect on IA memory regardless of the footshock intensity used during training ?

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Fig. 1

IA

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Propranolol administrated systemically immediately after retrieval has no effect on IA memory regardless of the footshock intensity used during training

Question: Propranolol administered systemically 30 min before

retrieval affects reconsolidation of IA ?

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Fig. 1

IA

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Propranolol administered systemically 30 min before retrieval affects retrieval but not reconsolidation of IA

Question: Propranolol administered systemically after retrieval

disrupts cued and contextual FC reconsolidation ?

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Fig. 2

A

FC

AA

A A

A AA

A

B B B

B BB

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Propranolol administered systemically after retrieval disrupts both cued and contextual FC reconsolidation: Effect of retrieval modality

Question:

Propranolol disrupts freezing and inhibitory avoidance memory ?

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Inhibitory avoidance (IA)+Cue

Training

IA test

Latency Freezing

Cue test

19Context B

Fig. 3

B

B

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Propranolol disrupts freezing but not inhibitory avoidance memory

IA FC

Before Retrieval

0.9mA0.6mA

After Retrieval

0.6mA0.25mA

IA+CUE

0.6mA 0.9mA

Latency

Latency

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Conclusion & DiscussionConclusion & Discussion

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Conclusion Conclusion

The efficacy of systemic administration of propranolol in disrupting the reconsolidation of fear memories is not general, but limited to some types of fear memories.

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results show that propranolol administered after retrieval does not affect the reconsolidation of IA, whereas as also shown by previous authors

(Debiec and LeDoux 2004; Abrari et al. 2007)

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Our data on the effect of propranolol on auditory FC confirm previous results obtained by Debiec and LeDoux (2004)

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A previous study from Przybyslawski et al. (1999), who also used systemic administration of propranolol similar to that employed in our experiments (10 mg/kg, i.p. immediately after reactivation by testing), concluded that propranolol disrupts the reconsolidation of IA.

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IA Place two paws Place four paws

footshock 0.25mA 0.25~0.9mA

inject Brain Blood

Thanks for your attention!Thanks for your attention!

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