Developmental lead exposure differentially alters the susceptibility to chemoconvulsants in rats.
Sprague-Dawley rats were exposed to lead (Pb) acetate (0.2% w/v) in drinking water from postnatal day (PN) 1 through PN 25 followed by discontinuing Pb exposure for 25 days. The convulsion signs produced by the i.v. infusion of convulsants were observed at PN 25 and PN 50. Pb exposure significantly decreased pentylenetetrazol (PTZ)-, picrotoxin (PIC)-, and strychnine (STRY)-induced, but increased N-methyl-D-aspartate (NMDA) and 4-aminopyridine (4-AP)-induced convulsion thresholds at PN 25. After rehabilitation, the Pb-induced changes in PTZ-, NMDA- and 4-AP- induced convulsions persisted till PN 50. In contrast, the thresholds for PIC- and STRY-induced convulsions were reversed to an increase at PN 50. Blood Pb concentrations were 46.9 +/- 6.8 and 11.4 +/- 1.1 microg/dl at PN 25 and PN 50, respectively. The results demonstrate that developmental Pb exposure does not result in a global and persistent lowering of threshold in response to convulsive stimuli and the Pb-induced changes may be due to a selective modulation of inhibitory and excitatory neurotransmission depending on age and Pb concentration in blood.
Chen
Hwei Hsien
HH
Institute of Toxicology, Tzu Chi University, 701 Section 3, Chung-Yang Road, 970, Hualien, Taiwan. hwei@mailtcu.edu.tw
Chan
Ming Huan
MH
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D003292:Convulsants / Q000494:pharmacology / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004326:Drinking; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D005618:Fresh Water; D007854:Lead / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced*
D003292:Convulsants; D009942:Organometallic Compounds; D007854:Lead