Abstract
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 μg/dl) and inhibiting AMPH-induced cFOS expression at higher levels of exposure (mean blood lead level 47.4 ± 2.6 μg/dl).
Footnotes
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This work was supported by National Institute of Environmental Health Science Grant ES09977 (to D.K.P.) and by the Department of Pharmaceutical Sciences at Wayne State University.
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DOI: 10.1124/jpet.103.063941.
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ABBREVIATIONS: DA, dopamine; ADHD, attention-deficit hyperactivity disorder; cFOS-IR, cFOS-immunoreactivity; NMDA, N-methyl-d-aspartate; CREB, cAMP response element-binding protein; Con, control; Veh, vehicle; AMPH, amphetamine; ANOVA, analysis of variance; SKF-38393, (±)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride.
- Accepted April 26, 2004.
- Received December 5, 2003.
- The American Society for Pharmacology and Experimental Therapeutics
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