Inorganic lead exposure in the rat activates striatal cFOS expression at lower blood levels and inhibits amphetamine-induced cFOS expression at higher blood levels.
The impact of inorganic lead exposure on dopamine (DA) neurotransmission in the basal ganglia was examined. Amphetamine (AMPH)-induced cFOS immunoreactivity (cFOS-IR) in the striatum was determined after a 3-week exposure to lead acetate (0, 50, or 250 ppm). On the 21st day of lead exposure, rats were challenged with AMPH (4 mg/kg i.p.) or saline vehicle (Veh) and were assayed for presence of cFOS-IR. In the untreated control (Con) group, AMPH challenge (Con/AMPH) increased cFOS-IR expression by approximately 35-fold over Veh challenge (Con/Veh) (P < 0.01). In the Pb50/Veh group, cFOS-IR expression was approximately 7-fold greater than in the Con/Veh group (P < 0.05). Given that there was negligible cFOS-IR expression in the Con/Veh group, this indicates that the Pb50 exposure induced cFOS expression. The increase in cFOS-IR in the Pb50/AMPH was also significant (P < 0.01), but it was not different from the Con/AMPH (P > 0.20). Neither the Pb250/Veh group nor the Pb250/AMPH group had a significant increase in cFOS-IR relative to Con/Veh (P > 0.20). These results indicate that chronic 50 ppm lead exposure induced a low but statistically significantly level of cFOS gene activation and that it did not affect the AMPH-induced cFOS activation. However, chronic 250 ppm lead exposure inhibited AMPH-induced activation of cFOS in the striatum by about 89%. Therefore, lead is capable of both activating cFOS expression at low levels of exposure (mean blood lead level 21.6 +/- 1.9 microg/dl) and inhibiting AMPH-induced cFOS expression at higher levels of exposure (mean blood lead level 47.4 +/- 2.6 microg/dl).
Lewis
Mark W
MW
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave, Detroit, MI 48202, USA. aa3529@wayne.edu
Pitts
David K
DK
D000661:Amphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000097:blood*; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015533:Transcriptional Activation
D009942:Organometallic Compounds; D016760:Proto-Oncogene Proteins c-fos; D000661:Amphetamine; C008261:lead acetate