Periodical reactivation under the effect of caffeine attenuates fear memory expression in rats

Lizeth K Pedraza,Rodrigo O Sierra,Fernanda N Lotz,Lucas De Oliveira Alvares

doi:10.1038/s41598-018-25648-6

Lizeth K Pedraza, Rodrigo O Sierra + Show 2 more

Open Access

https://doi.org/10.1038/s41598-018-25648-6

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Journal: Scientific Reports	Publication Date: May 8, 2018
Citations: 17	License type: open-access

Affiliation: Universidade Federal do Rio Grande do Sul

Abstract

In the last decade, several studies have shown that fear memories can be attenuated by interfering with reconsolidation. However, most of the pharmacological agents used in preclinical studies cannot be administered to humans. Caffeine is one of the world’s most popular psychoactive drugs and its effects on cognitive and mood states are well documented. Nevertheless, the influence of caffeine administration on fear memory processing is not as clear. We employed contextual fear conditioning in rats and acute caffeine administration under a standard memory reconsolidation protocol or periodical memory reactivation. Additionally, potential rewarding/aversion and anxiety effects induced by caffeine were evaluated by conditioning place preference or open field, respectively. Caffeine administration was able to attenuate weak fear memories in a standard memory reconsolidation protocol; however, periodical memory reactivation under caffeine effect was necessary to attenuate strong and remote memories. Moreover, caffeine promoted conditioned place preference and anxiolytic-like behavior, suggesting that caffeine weakens the initial learning during reactivation through counterconditioning mechanisms. Thus, our study shows that rewarding and anxiolytic effects of caffeine during fear reactivation can change the emotional valence of fear memory. It brings a new promising pharmacological approach based on drugs widely used such as caffeine to treat fear-related disorders.

Highlights

In the last decade, several studies have shown that fear memories can be attenuated by interfering with reconsolidation
We evaluated the effects of systemic caffeine administration before a standard memory reconsolidation protocol
Animals were submitted to weak contextual fear conditioning (CFC) training (4 footshocks of 0.4 mA/2-s) on day 1 and injected systemically with vehicle or caffeine 20 mg/kg, 30-min before memory reactivation on day 3, and tested 24-h later in a drug-free condition

Summary

Introduction

Several studies have shown that fear memories can be attenuated by interfering with reconsolidation. Our study shows that rewarding and anxiolytic effects of caffeine during fear reactivation can change the emotional valence of fear memory It brings a new promising pharmacological approach based on drugs widely used such as caffeine to treat fear-related disorders. Novel therapeutic strategies that target memory reconsolidation have emerged with promising results to attenuate persistent fear memories This paradigm involves the transient labilization of the memory trace induced by a retrieval/reactivation session that makes the original memory susceptible to pharmacological and behavioral modifications[1,2,3]. Conflicting reports reveal that caffeine may enhance or disrupt memory acquisition, consolidation and retrieval across a variety of fear memory tests[21,22,23,24,25,26]

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