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Brain Sci. 2013, 3(3), 1128-1152; doi:10.3390/brainsci3031128
Article

Developmental Neurotoxicity of Alcohol and Anesthetic Drugs Is Augmented by Co-Exposure to Caffeine

1
, 2
 and 2,*
Received: 22 April 2013; in revised form: 6 July 2013 / Accepted: 11 July 2013 / Published: 30 July 2013
(This article belongs to the Special Issue Ethanol Neurotoxicity)
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Abstract: Anesthetic and anti-epileptic drugs used in pediatric and obstetric medicine and several drugs, including alcohol, that are abused by pregnant women, trigger widespread neuroapoptosis in the developing brain of several animal species, including non-human primates. Caffeine (CAF) is often administered to premature infants to stimulate respiration, and these infants are also exposed simultaneously to anesthetic drugs for procedural sedation and/or surgical procedures. Pregnant women who abuse alcohol or other apoptogenic drugs also may heavily consume CAF. We administered CAF to infant mice alone or in combination with alcohol, phencyclidine, diazepam, midazolam, ketamine, or isoflurane, which are drugs of abuse and/or drugs frequently used in pediatric medicine, and found that CAF weakly triggers neuroapoptosis by itself and markedly potentiates the neuroapoptogenic action of each of these other drugs. Exposure of infant mice to CAF + phencyclidine resulted in long-term impairment in behavioral domains relevant to attention deficit/hyperactivity disorder, whereas exposure to CAF + diazepam resulted in long-term learning/memory impairment. At doses used in these experiments, these behavioral impairments either did not occur or were substantially less pronounced in mice exposed to CAF alone or to phencyclidine or diazepam alone. CAF currently enjoys the reputation of being highly beneficial and safe for use in neonatal medicine. Our data suggest the need to consider whether CAF may have harmful as well as beneficial effects on the developing brain, and the need for research aimed at understanding the full advantage of its beneficial effects while avoiding its potentially harmful effects.
Keywords: CAF; alcohol; anesthetic drugs; neuroapoptosis; developing brain CAF; alcohol; anesthetic drugs; neuroapoptosis; developing brain
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Yuede, C.M.; Olney, J.W.; Creeley, C.E. Developmental Neurotoxicity of Alcohol and Anesthetic Drugs Is Augmented by Co-Exposure to Caffeine. Brain Sci. 2013, 3, 1128-1152.

AMA Style

Yuede CM, Olney JW, Creeley CE. Developmental Neurotoxicity of Alcohol and Anesthetic Drugs Is Augmented by Co-Exposure to Caffeine. Brain Sciences. 2013; 3(3):1128-1152.

Chicago/Turabian Style

Yuede, Carla M.; Olney, John W.; Creeley, Catherine E. 2013. "Developmental Neurotoxicity of Alcohol and Anesthetic Drugs Is Augmented by Co-Exposure to Caffeine." Brain Sci. 3, no. 3: 1128-1152.



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