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NEUROPHARMACOLOGY

Inorganic Lead Exposure in the Rat Activates Striatal cFOS Expression at Lower Blood Levels and Inhibits Amphetamine-Induced cFOS Expression at Higher Blood Levels

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan

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).

Address correspondence to: Dr. Mark W. Lewis, Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave, Detroit, MI 48202. E-mail: aa3529{at}wayne.edu

This article has been cited by other articles:

				M. Tavakoli-Nezhad and D. K. Pitts Postnatal Inorganic Lead Exposure Reduces Midbrain Dopaminergic Impulse Flow and Decreases Dopamine D1 Receptor Sensitivity in Nucleus Accumbens Neurons J. Pharmacol. Exp. Ther., March 1, 2005; 312(3): 1280 - 1288. [Abstract] [Full Text] [PDF]