ORIGINAL RESEARCH
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
More details
Hide details
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
KEYWORDS
ABSTRACT
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).