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ToxSci Advance Access published online on November 15, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl168
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received September 18, 2006
Accepted November 10, 2006

Neurotoxicology

Effects of Toluene Exposure During Brain Growth Spurt on GABAA Receptor-Mediated Functions in Juvenile Rats

Jeng-Lu Liu 1 #, Yi-Ruu Lin 2 #, Ming-Huan Chan 3, and Hwei-Hsien Chen 4 *

1 Institute of Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, 970, Taiwan; Buddhist Tzu Chi General Hospital, 707, Sec. 3, Chung Yang Rd., Hualien 970, Taiwan
2 Institute of Medical Sciences, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, 970, Taiwan
3 Institute of Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, 970, Taiwan
4 Institute of Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, 970, Taiwan; Institute of Medical Sciences, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, 970, Taiwan

* To whom correspondence should be addressed.
Hwei-Hsien Chen, E-mail: hwei{at}mail.tcu.edu.tw


  Abstract

Toluene is a commonly abused inhalant. Its neurobiological effects are, at least in part, mediated by GABAA receptors. Since GABAA receptor function is critical during brain development, the long-term effects of toluene exposure during brain growth spurt were investigated. Spargue-Dawley male rats were administered with toluene (500 mg/kg, i.p.) on postnatal day (PN) 4~9. Behavioral and electrophysiological measures and the levels of mRNA expression of GABAA receptor subunits were examined on PN 28-32. The seizure sensitivity induced by bicuculline (a GABAA receptor antagonist), methyl {beta}-carboline-3-carboxylate ({beta}-CCM, inverse agonists of the GABAA/benzodiazepine receptor), but not 3-mercaptopropionic acid (3-MPA, a glutamate decarboxylase inhibitor) were enhanced by toluene exposure. Toluene exposure had no effect on the performance in the elevated plus-maze and rotarod test, but reduced the responses to diazepam in these two tests. In vitro intracellular electrophysiological recordings employing brain slices from rats treated with toluene demonstrated a significant decrease in GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) in CA1 neurons, but an increased response to GABA perfusion. The relative abundance of the mRNAs encoding various subunits of GABAA receptor ({alpha}1, {alpha}2, {alpha}4, {alpha}5, {alpha}6, {beta}2, {beta}3, {gamma}2S, {gamma}2L) was examined in four brain regions (hippocampus, striatum, cortex, and cerebellum) by semiquantitative reverse transcription-PCR (RT-PCR). These results demonstrated subunit- and brain area-selective alterations in GABAA receptors after toluene exposure during brain growth spurt. The alterations in GABAA receptors might be associated with the neurobehavioral disturbance in offspring of toluene-abusing women.

Keywords: Toluene; brain growth spurt; GABAA receptors; electrophysiology; behavior.

#Contributed equally to this work


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[Abstract] [Full Text] [PDF]


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