The profound effects of numbing agents

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The profound effects of numbing agents

http://www.eurekalert.org/pub_releases/2008-12/asfb-tpe121108.php

A large proteomics study on the brains of newborn mice provides more

evidence that numbing drugs often used in obstetric or pediatric

medicine can have profound and long-term negative effects, even after

minimal exposure.

This study, appearing in the December issue of Molecular and Cellular

Proteomics, highlights the delicate state of the developing nervous

system and reinforces the use of caution when administering

sedatives, anesthetics, and anti-convulsants to pregnant women or

infants.

Compounds that either block excitatory NMDA receptors or activate

inhibitory GABA receptors in the brain are clinically useful as

anesthetics or for treating disorders like seizures and insomnia.

However, just like other chemicals that produce similar mind-soothing

effects (e.g. alcohol), excessive use can be detrimental –

particularly in still-developing individuals.

To examine how far-reaching the physiologic effects of such 'numbing'

drugs (sedatives, hypnotics, analgesics) are, Kaindl and

colleagues treated 6-day old mice with two doses of either the NMDA

receptor blocker dizocilpine or the GABA receptor activator

Phenobarbital and then analyzed subsequent changes in brain protein

expression.

They observed both acute and sustained effects, with protein changes

in the cerebral cortex (the area controlling memory, thought,

awareness, and language) evident after just 24 hours, and these

changes were still present one week and one month after the one-day

drug treatment. The affected proteins are involved in crucial

processes like cell growth, cell death, and the formation of neural

circuits (In another recent study, the authors were able to confirm

that such drug treatment negatively influences learning and memory).

A similar drug dose given to adult mice did not produce such changes,

which the authors note clearly shows how susceptible infant brains

are compared to adults. Importantly, this study shows that drug

overuse on even one occasion (for example, during the delivery

procedure) can have long-term implications.