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ToxSci Advance Access originally published online on October 20, 2007
Toxicological Sciences 2008 101(2):286-293; doi:10.1093/toxsci/kfm264
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Toluene Exposure during the Brain Growth Spurt Reduced Behavioral Responses to Nicotine in Young Adult Rats: A Potential Role for Nicotinic Acetylcholine Receptors in Fetal Solvent Syndrome

Ming-Huan Chan*,{dagger},2, Yu-Chi Tang*,{ddagger},2, Te-Hsiung Chien* and Hwei-Hsien Chen*,1

* Graduate Institute of Pharmacology and Toxicology {dagger} Department of Pharmacology, Tzu Chi University, Hualien 970, Taiwan {ddagger} Mackay Memorial Hospital, Taipei 104, Taiwan

1 To whom correspondence should be addressed at Institute of Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien 970, Taiwan. Fax: 886-3-856-1465. E-mail: hwei{at}mail.tcu.edu.tw.

Received September 3, 2007; accepted October 15, 2007


  Abstract

Toluene, an industrial organic solvent, is voluntarily inhaled as drug of abuse. Toluene has been shown to inhibit the nicotinic acetylcholine receptors. Nicotinic receptors play an important role in brain development during brain growth spurt and early adolescence. The long-term effects of neonatal and adolescent toluene exposure on behavioral responses to nicotine in early adulthood were compared. Sprague-Dawley male and female rats were treated with toluene (500 mg/kg, ip) or corn oil daily over postnatal day (PN) 4–9 or 25–30. Nicotine-induced hypothermia, antinociception, and seizure activity were examined during PN 56–60. Toluene exposure during the brain growth spurt, but not adolescence, reduced the behavioral responses to nicotine in young adult rats. However, the levels of {alpha}4, {alpha}7, and β2 nicotinic receptors were not altered in the frontal cortex, striatum, thalamus, hippocampus, and cerebellum by neonatal toluene exposure. These results indicate that toluene exposure during the brain growth spurt produces long-term changes in nicotine sensitivity, which may be unrelated to the total expression levels of {alpha}4, {alpha}7, and β2 nicotinic receptors. The alterations in nicotine sensitivity may be related to the neurobehavioral disturbance associated with fetal solvent syndrome.

Key Words: toluene; development; nicotinic acetylcholine receptor.

2 These authors contributed equally to this study.


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