title: Neonatal toluene exposure selectively alters sensitivity to different chemoconvulsant drugs in juvenile rats.
abstract: Toluene is an abused solvent widely used in several commercial products. Recent evidence indicates that this solvent is a noncompetitive inhibitor of N-methyl-D-aspartate (NMDA) receptors and enhances gamma-aminobutyric acid(A) (GABA(A)) receptor-mediated synaptic currents. Since NMDA and GABA(A) receptors have been implicated in seizures, this study investigated whether toluene exposure during synaptogenesis period alters the NMDA and GABA(A) receptor-mediated seizure susceptibility in juvenile rats. Neonatal rats were administered toluene (1 g/kg ip) daily over postnatal days (PN) 4-9. Rats were administered NMDA (10 mg/ml), picrotoxin (2 mg/ml), pentylenetetrazol, (5 mg/ml) and 4-aminopyridine (4-AP; 2 mg/ml) via timed tail vein infusion on PN 34-36. Toluene exposure increased sensitivity to NMDA, picrotoxin and pentylenetetrazol, but did not affect 4-aminoyridine-induced seizures in both male and female rats. These results suggest that toluene may possess a risk to the developing brain by inducing a long-term alteration in the function of NMDA and GABA(A) receptors.
authors.affiliation: Institute of Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien 970, Taiwan, ROC. hwei@mail.tcu.edu.tw
authors.forename: Hwei-Hsien
authors.initials: HH
authors.lastname: Chen
authors.forename: Yeh-Fu
authors.initials: YF
authors.lastname: Lee
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D003292:Convulsants / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity; D004357:Drug Synergism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D012640:Seizures / Q000097:blood / Q000139:chemically induced*; D014050:Toluene / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D003292:Convulsants; D018690:Excitatory Amino Acid Agonists; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D014050:Toluene