The role of N-methyl-D-aspartate receptors in neurobehavioral changes induced by toluene exposure during synaptogenesis.
Toluene abuse during pregnancy results in newborns with fetal solvent syndrome. N-Methyl-D-aspartate (NMDA) receptor has been identified as a target site for toluene. Since the normal function of NMDA receptor is critical for synaptogenesis, the long-term effects of toluene exposure during synaptogenesis on the neurobehavioral function and the expression of NMDA receptor subunits (NR1, NR2A, and NR2B) were examined. Rats exposed to l g/kg of toluene (i.p.) over postnatal days 4 to 9 were found to exhibit reduction in body weight, NMDA-induced seizure thresholds, and MK-801-induced hyperlocomotor activity. Furthermore, immunoblotting and immunohistochemical analysis revealed a significant increase in NR2A subunit expression in the hippocampus and cerebellum of toluene-exposed rats on PN30. These results suggest that the region-specific changes in the expression of NMDA receptor subunits may play a role in the neurobehavioral dysfunction following toluene exposure during synaptogenesis.
Chen
Hwei-Hsien
HH
Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan. hwei@mail.tcu.edu.tw
Lee
Yeh-Fu
YF
Chan
Ming-Huan
MH
Lo
Pi-Shih
PS
D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development*; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D014050:Toluene / Q000008:administration & dosage*
D016194:Receptors, N-Methyl-D-Aspartate; D014050:Toluene