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Developmental Lead Exposure Impairs Anxiolytic-Like Effects of Diazepam and 8-OH-DPAT in Male Wistar Rats
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Developmental Lead Exposure Impairs Anxiolytic-Like Effects of Diazepam and 8-OH-DPAT in Male Wistar Rats
P. Nowak1, R. M. Kostrzewa2, B. Adamus-Sitkiewicz1, R. Brus1
1Department of Pharmacology, Medical University of Silesia, Jordana 38, 41-808 Zabrze, Poland
2Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA
Pol. J. Environ. Stud. 2008;17(5):751–756
The effects of developmental lead (Pb2+) exposure on the anxiolytic-like effect of diazepam (5.0 mg/kg IP) and 8-OH-DPAT (0.3 mg/kg IP) were studied. Wistar dams were exposed to 250 ppm lead acetate in drinking water during pregnancy. Control rats were derived from dams that consumed tap water, and had no exposure to Pb2+ afterwards. Male offspring were tested at the age of 12 weeks. We studied the anxiolytic-like effect of diazepam and 8-OH-DPAT in an elevated plus maze device and the Vogel conflict test. Diazepam in doses of 5.0 mg/kg IP significantly increased the percentage of time spent on open arms in control rats being without effect in Pb2+-exposed animals. 8-OH-DPAT 0.3 mg/kg IP increased the percentage of time spent on open arms in both experimental groups (control and Pb2+), but the anxiolytic-like effect was much more pronounced in Pb2+-intoxicated animals. The benzodiazepine anxiolytic diazepam produced a significant effect in the Vogel conflict test in control rats. A 5.0 mg/kg dose of those drugs caused a significant increase in the number of electric shocks rats received. In the ontogenetically Pb2+-exposed rats diazepam also augmented the number of shocks accepted, but this effect was much less pronounced than in control animals. Conversely, 8-OH-DPAT at doses of 0.3 mg/kg IP was without effect in both tested groups as far as the anticonflict effect is concerned. The results of the present report demonstrated that exposure to Pb2+ during pregnancy induced hypersensitivity to 5-HT1A agonist mediated anxiolytic-like effect but attenuated that of benzodiazepine (diazepam).
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