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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

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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.

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Abbreviations

Bw:

Body weight

DA:

Dopamine

D1-Rs:

Dopamine D1-like receptors

D2-Rs:

Dopamine D2-like receptors

DAT:

Dopamine transporter

DOPAC:

Dihydroxyphenylacetic acid

GD:

Gestational day

PCB153:

2,2′,4,4′,5,5′-Hexachlorobiphenyl

HVA:

Homovanillic acid

MeHg:

Methylmercury

PCB:

Polychlorinated biphenyl

PND:

Postnatal day

5-HT:

Serotonin/5-hydroxytriptamine

TH:

Tyrosine hydroxylase

VMAT:

Vesicular monoamine transporter

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Acknowledgments

This work was supported by the EU Grant DEVNERTOX (FOOD-CT-2003-506143) and by grants from the Italian Ministry of Health. The authors wish to acknowledge Mr. Davide Acerbi for his excellent technical assistance.

Conflict of interest

The authors declare that there are no conflict of interest.

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Authors and Affiliations

  1. Toxicology Division, Research Center for Occupational and Environmental Toxicology, IRCCS Salvatore Maugeri Foundation, Institute of Pavia, Via Maugeri, 10, 27100, Pavia, Italy

    Teresa Coccini, Anna F. Castoldi & Luigi Manzo

  2. Toxicology Division, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy

    Elisa Roda & Luigi Manzo

  3. Department of Clinical Medicine, Nephrology and Health Sciences, Laboratory of Industrial Toxicology, University of Parma, Parma, Italy

    Diana Poli, Matteo Goldoni, Maria Vittoria Vettori & Antonio Mutti

  4. ISPESL Research Centre, University of Parma, Parma, Italy

    Diana Poli, Matteo Goldoni & Maria Vittoria Vettori

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  1. Teresa Coccini
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  2. Elisa Roda
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  3. Anna F. Castoldi
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  4. Diana Poli
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  7. Antonio Mutti
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  8. Luigi Manzo
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Correspondence to Teresa Coccini.

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Coccini, T., Roda, E., Castoldi, A.F. et al. 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. Arch Toxicol 85, 1281–1294 (2011). https://doi.org/10.1007/s00204-011-0660-y

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