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Developmental Neurotoxicity of Alcohol and Anesthetic Drugs Is Augmented by Co-Exposure to Caffeine
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA
* Author to whom correspondence should be addressed.
Received: 22 April 2013; in revised form: 6 July 2013 / Accepted: 11 July 2013 / Published: 30 July 2013
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
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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.
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.
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.