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

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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.
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