Influence of Perinatal Polychlorinated Biphenyl or Thiouracil on Dopamine Function

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Objective: Dopamine function is sensitive to toxin exposure. The environmental toxin polychlorinated biphenyl (PCB) alters dopamine physiology in several, harmful ways. Intermediary signals include thyroid hormones as PCB exposure alters thyroid function leading to changes in dopamine neurochemistry. To compare PCB and thyroid alterations directly, we exposed rats perinatally to either PCB (25 ppm) or thiouracil (THIO; 0.625%) from gestational day 1 to separation from the dam at postnatal day (PND) 25 and examined a set of tests sensitive to dopamine function.

Methods: We measured behaviors including prepulse inhibition (PPI) of the acoustic startle response (ASR) in adulthood (60-90 PND) and ultrasonic vocalizations (USVs) during pup and adult periods. Dopamine levels in striatum were estimated using tyrosine hydroxylase immunohistochemistry and thyroid hormone levels were assayed in adulthood.

Results: Animals exposed to thiouracil had significantly elevated startle response and impaired PPI relative to controls and PCB exposed animals. This group also had significant reductions in both USV emission during PPI and tyrosine hydroxylase staining within striatum. Conversely, PCB exposure during the perinatal period did not lead to alterations in gating or dopamine levels in adulthood. Similar to previous studies using perinatal exposure to PCB or THIO, thyroid hormone levels were unchanged (THIO group) relative to controls or actually increased (PCB group) by adulthood.

Conclusion: The findings support an important role for thyroid function in dopamine-dependent behaviors. Results suggest PCB exposure leads to different outcomes in comparison to direct thyroid manipulations suggesting PCB exposure has distinct mechanisms of developmental hormone dysfunction and potential compensatory changes in response to endocrine disruption.

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The work was partially funded by an award to HCC and LAM (the NIH/HHS/. United States R03 HD0536 92/HD/NICHD). In addition the work was partly funded by the departments of Biological Sciences and Psychology and the Center for Undergraduate Research at Bowling Green State University. We would like to thank Mr. Andy Wickiser for his help in designing apparatus and programming the prepulse inhibition chambers and undergraduate research assistants Micheal Stoffer and Kyle Shaw for their help in running the test sessions for prepulse inhibition.

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Correspondence to Howard C. Cromwell.

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All procedures were approved by and performed according to the guidelines established by the Bowling Green State University Institutional Animal Care and Use Committee (IACUC) and United States Animal Welfare Act (7 U.S.C. §2131 et. seq.) as provided by the United States Research Council's Guide for the Care and Use of Laboratory Animals.

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Cynthia L. Toth declares that she has no conflicts of interest. David E. Mankin declares that he has no conflicts of interest. Katie A. Hiler declares that she has no conflicts of interest. Nicholas A.F. Baldwin declares that he has no conflicts of interest. Lee A. Meserve declares that he has no conflicts of interest. Howard C. Cromwell declares that he has no conflicts of interest.

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Toth, C.L., Mankin, D.E., Hiler, K.A. et al. Influence of Perinatal Polychlorinated Biphenyl or Thiouracil on Dopamine Function. Toxicol. Environ. Health Sci. 11, 283–294 (2019).

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  • Emotion
  • Endocrine disruption
  • Gating
  • Startle
  • Thyroid