Abstract
Experimental evidence in humans and non-human animals suggests that the administration of propranolol shortly after the retrieval of an emotional memory can lead to an attenuation of its later expression, a phenomenon known as post-reactivation amnesia. Using more potent amnestic drugs, post-reactivation amnesia has been shown in animals to be reversible by re-administration of the drug prior to memory retention testing. The latter finding suggests that, at least under some circumstances, post-reactivation amnesia may not reflect a disruption of reconsolidation (i.e., a memory storage deficit) but an acquired state-dependency of memory expression (i.e., a memory retrieval deficit that is relieved when the drug state is recreated during testing). We conducted a double-blind, placebo-controlled study to investigate whether the previously established amnestic effects of post-reactivation propranolol administration on memory retention in humans may similarly reflect a retrieval deficit. In four groups of participants, fear memories were first established through differential fear conditioning. One day later, a single presentation of the CS+ without shock was used to reactivate the memory in three of the four groups, followed by the administration of 40 mg Propranolol HCl (Groups PrPl and PrPr) or placebo (Group PlPl). Memory was not reactivated in the fourth group (Group NR). Another 24 h later, Propranolol HCl (Group PrPr) or placebo (Groups PrPl, PlPl, and NR) was again administered, followed by a test of memory retention (extinction testing) and recovery (reinstatement testing). We did not observe any effects of post-reactivation propranolol on memory retention; conditioned responding was similar for all groups at the start of retention testing and similarly sensitive to recovery through reinstatement. We did observe an acute effect of propranolol administration on fear-potentiated startle responding during retention testing in Group PrPr, where participants exhibited attenuated startle responses during extinction testing but similar sensitivity to reinstatement as participants in the other groups. While our findings fail to corroborate previous reports of propranolol-induced post-reactivation amnesia in humans, they do point to acute effects of propranolol administration on extinction performance.
Highlights
Accumulating experimental evidence in animals and humans points to the dynamic, rather than stable, nature of memory
We investigated the effects of postreactivation propranolol administration on fear memory expression
We aimed to examine whether previous observations of propranolol-induced post-reactivation amnesia in humans reflect a disruption of reconsolidation, and a loss of the original memory, or are due to incongruency of the internal state during memory retention testing with the drug-induced state created upon memory reactivation preventing successful retrieval
Summary
Accumulating experimental evidence in animals and humans points to the dynamic, rather than stable, nature of memory. Blocking protein synthesis while a memory is malleable will theoretically prevent it from being restored, yielding retroactive amnesia in further tests of memory expression (i.e., memory storage deficit) (Tronson and Taylor, 2007). Reports of reconsolidation blockade have involved administration of very powerful proteinsynthesis inhibitors, such as anisomycin (Nader et al, 2000) or cycloheximide (Duvarci et al, 2005; Gisquet-Verrier et al, 2015). At doses tailored to yield observations of retrograde amnesia, these drugs would be severely toxic to humans (Gisquet-Verrier et al, 2015; Beckers and Kindt, 2017). Debiec and LeDoux (2004), induced amnesia in rats by post-reactivation administration of propranolol, a β-adrenergic receptor antagonist. At a similar relative dose as used in rats, propranolol is perfectly safe for human use
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