Developmental exposure to methylmercury and 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) affects cerebral dopamine D1-like and D2-like receptors of weanling and pubertal rats

Abstract

MeHg (0.5 mg/kg/day) and/or PCB153 (5 mg/kg/day) effects, administered orally to rat dams (GD7-PND21), were explored in PND21 and PND36 offspring brain in terms of density (Bmax) and affinity (Kd) of dopamine D1-like (D1-Rs) and D2-like receptors (D2-Rs), by saturation binding studies. D1-Rs decreased density in both cortex and striatum (15-30%) by MeHg and PCB153, either alone or combined, without additivity in PND21 males. Changes disappeared by PND36. In females, only MeHg caused a 15% Bmax decrease in striatum. D2-Rs enhanced density (23-50%) and reduced affinity in cortex to a similar extent by all treatments in both weanling and pubertal males. Affinity was also decreased in females by all types of exposure at both ages, while density was enhanced by PCB153 only in a delayed manner (PND36). No changes were detected in striatum. In MeHg and MeHg + PCB153 pup cortex, Hg concentrations ranged, on PND21, between 0.25 and 0.89 and 0.94-1.40 μg/g tissue, respectively, and were 5- to sixfold lower 2 weeks later. PCB153 levels, in PCB153 ± MeHg treated rats, were about 15 μg/g tissue (PND21) and 4-8 μg/g tissue (PND36). In striatum, the Hg and PCB153 concentrations were similar to those in cortex. Brain kinetics trend also applied to blood PCB153 or Hg levels. Perinatal exposure to MeHg and/or PCB153 affects D1- and D2-Rs in a gender-, time-, and brain area-dependent manner. Combined treatment does not exacerbate the neurochemical effects of the individual compounds.