Neonatal toluene exposure selectively alters sensitivity to different chemoconvulsant drugs in juvenile rats.
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.
Chen
Hwei-Hsien
HH
Institute of Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien 970, Taiwan, ROC. hwei@mail.tcu.edu.tw
Lee
Yeh-Fu
YF
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
D003292:Convulsants; D018690:Excitatory Amino Acid Agonists; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D014050:Toluene