Implicit aversive memory under anaesthesia in animal models: a narrative review

Abstract

Explicit memory after anaesthesia has gained considerable attention because of its negative implications, while implicit memory, which is more elusive and lacks patients' explicit recall, has received less attention and dedicated research. This is despite the likely impact of implicit memory on postoperative long-term well-being and behaviour. Given the scarcity of human data, fear conditioning in animals offers a reliable model of implicit learning, and importantly, one where we already have a good understanding of the underlying neural circuitry in awake conditions. Animal studies provide evidence that fear conditioning occurs under anaesthesia. The effects of different anaesthetics on memory are complex, with different drugs interacting at different stages of learning. Modulatory suppressive effects can be because of context, specific drugs, and dose dependency. In some cases, low doses of general anaesthetics can actually lead to a paradoxical opposite effect. The underlying mechanisms involve several neurotransmitter systems, acting mainly in the amygdala, hippocampus, and neocortex. Here, we review animal studies of aversive conditioning under anaesthesia, discuss the complex picture that arises, identify the gaps in knowledge that require further investigation, and highlight the potential translational relevance of the models.

Mouse Anesthesia: The Art and Science

“…Samuel et al previously demonstrated there is a response difference between front and hind paw withdrawal, with the hind paw withdrawal being a more valuable indicator of a surgical anesthesia plane in mice. 13 During the initial anesthesia induction (depending on the type of anesthetic used, route of administration of anesthesia, mouse age and strain), the anesthesia plane will continuously evolve into a deeper plane. For example, when using injectable ket/xyl anesthesia in mice, it can require between 6 and 20 minutes to reach a surgical anesthesia plane depending on the mouse strain and route of administration.…”

“…In addition to an anesthetic’s ability to alter consciousness, anesthetics impact memory (ie, cause amnesia). 4 , 5 , 9–11 Though we have a limited ability to assess amnesia in animals, previous studies have shown amnesia secondary to anesthesia in a variety of animal species, including mice, 12 , 13 rats, 13 , 14 and zebrafish. 15 Thus, properly induced and conducted general anesthesia is expected to produce amnesia in laboratory animals.…”

Implicit Memory and Anesthesia: A Systematic Review and Meta-Analysis

“…The age-induced decline of implicit memory (e.g., priming) is less than the decline of explicit memory (e.g., recognition) [ 79 ]. Explicit memory and implicit memory involve different parts of the brain: while the hippocampus is necessary for explicit memory, the amygdala, a small structure located near the hippocampus, is essential for implicit memory formation [ 80 ]. A surgery-induced stress response causing elevated norepinephrine levels and amygdala activity (in addition to other regions) would facilitate the implicit learning of emotionally negative information presented during anesthesia [ 49 ].…”

“…On the other hand, most of the deep sedation regimens were based on propofol or midazolam, two γ-aminobutyric acid type A receptor agonists with an amnestic effect [ 80 ], which were administered in the absence of opioids and NMBAs, at a dosage to prevent a reaction following repeated or painful stimulation.…”

Dissociable learning processes, associative theory, and testimonial reviews: A comment on Smith and Church (2018)

“…Hence, conditioned taste aversion should be explicit by their definition-but this does not seem to be the case. For example, conditioned taste aversion in rats is still acquired when the illness-inducing outcome is delivered under general anesthesia (Bermudez-Rattoni et al, 1988;Samuel et al, 2018). Also, in humans undergoing cancer treatment, conditioned taste aversions are formed despite the patients being aware that their illness/nausea is produced by the treatment and not the novel foods eaten (Bernstein & Webster, 1980).…”