wang2010.pdf - Can J Anesth/J Can Anesth(2011...

THEME ISSUE: MECHANISMS OF ANESTHESIA
Inhibition of learning and memory by general anesthetics
Inhibition de l’apprentissage et de la me ´moire par les
anesthe ´siques ge ´ne ´raux
Dian-Shi Wang, MD, PhD
•
Beverley A. Orser, MD, PhD
Received: 25 July 2010 / Accepted: 15 November 2010 / Published online: 23 December 2010
Ó Canadian Anesthesiologists’ Society 2010
Abstract
Purpose Today’s general anesthetics were developed
empirically according to their ability to produce memory
blockade, analgesia, immobility, and unconsciousness.
Thus, a major outstanding question remains: How do
anesthetics produce their desirable behavioural end points
at the molecular level? Understanding the mechanisms
underlying memory blockade is of particular importance,
because some patients experience the unexpected recall of
events during anesthesia while others experience persistent
memory deficits in the postoperative period. This review
provides a brief summary of the acute memory-blocking
properties of general anesthetics and the neuronal sub-
strates that most likely contribute to memory loss.
Principal findings Studies in human volunteers and
laboratory animals have shown that the memory-blocking
properties of general anesthetics depend on the specific
drug, the dose, the type of memory, and the experimental
paradigm, as well as the species and age of the experi-
mental subject. The cellular substrates of memory blockade
include an increase in neuronal inhibition by c -aminobu-
tyric acid subtype A receptors, a decrease in excitatory
glutamatergic neurotransmission, and alterations in syn-
aptic plasticity.
Conclusions Anesthetics target different receptors and
brain regions to modify the various forms of memory. In the
hippocampus, extrasynaptic c -aminobutyric acid subtype A
receptors may play a particularly important role. Knowl-
edge regarding the molecular basis of memory blockade
may help to address memory disorders associated with the
anesthetic state.
Re
´sume ´
Objectif Les anesthe´siques ge´ne´raux actuels ont e´te´ mis
au point empiriquement en se fondant sur leur capacite´ a`
bloquer la me´moire ainsi qu’a` provoquer l’analge´sie,
l’immobilite´et l’inconscience. En raison de ce de´veloppement
empirique, une question cruciale demeure sans re´ponse:
comment les anesthe´siques produisent-ils leurs effets
de´sirables sur le comportement au niveau mole´culaire? La
compre´hension des me´canismes sous-jacents au blocage de
la me´moire est particulie`rement importante, e´tant donne´
que certains patients se souviennent de manie`re impre´vue
d’e´ve´nements ayant eu lieu pendant qu’ils e´taient sous
anesthe´sie, alors que d’autres souffrent de troubles de
me´moire persistants en pe´riode postope´ratoire. Ce
compte-rendu pre´sente brie`vement les proprie´te´s des
anesthe´siques ge´ne´raux sur le blocage aigu de la me´moire
ainsi que les substrats neuronaux qui contribuent tre`s
probablement a` la perte de me´moire.