Postweaning lead exposure enhances the stimulus properties of N-methyl-D-aspartate: possible dopaminergic involvement?
This study sought to determine whether previously reported Pb-induced biochemical changes in the NMDA receptor complex also resulted in changes in NMDA sensitivity in vivo. Rats chronically exposed to 0, 50 or 150 ppm Pb acetate in drinking water postweaning were trained to discriminate the stimulus properties of 30 mg/kg NMDA from saline using standard operant food-reinforced drug discrimination procedures. Following acquisition of the discrimination, various doses of NMDA, of the competitive antagonist CPP, the D2 antagonist spiperone and the D1 antagonist SCH23390 were substituted for the NMDA training dose and percent NMDA responding to each determined. In addition, the efficacy of CPP in antagonizing the NMDA stimulus was assessed. NMDA increased drug lever responding to levels > 90%, an effect antagonized by CPP. Spiperone substituted for NMDA, whereas SCH23390 engendered partial substitution and CPP only minimal substitution. Pb exposure did enhance NMDA sensitivity, as indicated by an increased frequency of full NMDA substitution at lower NMDA doses, although the effect size was somewhat modest. Pb exposure, at least at one dose, also attenuated the substitution of spiperone for NMDA, raising the possibility that dopaminergic systems may be involved in mediating Pb-induced changes in NMDA sensitivity.
Cory-Slechta
D A
DA
Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, New York 14642, USA.
Pokora
M J
MJ
Johnson
J L
JL
D000818:Animals; D004192:Discrimination, Psychological / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D007854:Lead / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology; D013134:Spiperone / Q000494:pharmacology*
D018492:Dopamine Antagonists; D018690:Excitatory Amino Acid Agonists; D009942:Organometallic Compounds; D016194:Receptors, N-Methyl-D-Aspartate; D007854:Lead; D013134:Spiperone; D016202:N-Methylaspartate; C008261:lead acetate