Effects of PCBs and PBDEs on response inhibition and dopaminergic signaling

Eubig, Paul

Permalink

https://hdl.handle.net/2142/45415 Copy

Description

Title

Effects of PCBs and PBDEs on response inhibition and dopaminergic signaling

Author(s)

Eubig, Paul

Issue Date

2013-08-22T16:39:30Z

Director of Research (if dissertation) or Advisor (if thesis)

Schantz, Susan L.

Doctoral Committee Chair(s)

Schantz, Susan L.

Committee Member(s)

• Ferguson, Duncan C.
• Flaws, Jodi A.
• Gulley, Joshua M.

Department of Study

Comparative Biosciences

Discipline

VMS - Comparative Biosciences

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• polychlorinated biphenyls
• polybrominated diphenyl ethers
• impulsive behavior
• developmental exposure
• dopamine
• dopamine transporter
• rats

Abstract

Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are persistent environmental contaminants that share physical and neurotoxic properties. Developmental PCB exposure has been associated with impulsive behavior in laboratory species and human cohorts, while little is known about whether PBDEs have similar effects. Both PCBs and PBDEs have been shown to perturb dopaminergic neurotransmission. The behavioral and neurochemical effects of PCBs parallel changes seen in children with attention deficit hyperactivity disorder (ADHD). The aims of this research were to further investigate the effects of PCBs and PBDEs on inhibitory control and dopaminergic signaling using a rodent model. The findings were anticipated to provide insight into the role that these environmental contaminants have on mechanisms and manifestations of impulsive behavior and provide insights as to whether exposure to PCBs and/or PBDEs may be a contributing factor in ADHD. Female Long Evans rats received daily oral doses of either 3 or 6 mg/kg of an environmentally-relevant PCB mixture, 11.4 or 22.8 mg/kg of the commercial PBDE solution DE-71, or corn oil vehicle (i.e., 5 treatment groups) from 4 weeks prior to breeding through weaning at postnatal day (PND) 21. Starting on PND 90, male-female pairs of offspring from each litter were tested on either a task that assesses impulsive action, differential reinforcement of low rates of responding (DRL) task, or a task that assesses impulsive choice, delay discounting (DD). After subjects were trained on either task, they received drug challenges with the D1/D2 receptor antagonist flupenthixol (FLU), amphetamine (AMPH), and then FLU/AMPH together. It was hypothesized that PCB or PBDE exposure would result in impulsive performance on both tasks, while during the drug trials there would be shifts in the dose-response curves so that performance on both tasks would be improved by AMPH and impaired by FLU to a greater extent than in controls. Tissue punches from 4 brain regions important for DRL and DD performance were collected at PND 90 from littermates of those being behaviorally tested. Western blots were performed on the punches to examine for differences in expression of dopamine transporter (DAT) between treatment groups. It was hypothesized that DAT expression would be reduced with PCB or PBDE exposure. PCB/PBDE-related effects on performance were not found on either the DRL or DD task, nor did the drug trials differentially alter the primary performance measures of impulsive behavior in treated groups relative to controls. The lack of effects of PCBs on DRL performance is in contrast to previous studies. However, some reasons why positive findings may have been obscured included potential insensitivity of the versions of the tasks used, particularly DD, in eliciting differences in impulsive behavior, and experimental manipulations in diet, contaminant dose, strain of rat or other unrecognized factors. In addition to the behavioral findings, DAT expression did not differ between treated and control subjects. This differs from the findings in previous in vivo and in vitro studies. However, DAT expression was examined 70 days after contaminant exposure ceased in the current study versus immediately after exposure ceased in prior studies. Thus, any possible changes in DAT expression could have resolved by the time brains were examined at PND 90 in the current study. While the current study did not allow insight into the role that PCBs and PBDEs have in impulsive behavior and dopaminergic signaling, a better understanding of experimental factors that can influence the outcome of in vivo and in vitro studies was gained.

Graduation Semester

2013-08

Permalink

http://hdl.handle.net/2142/45415

Copyright and License Information

Copyright 2013 Paul Eubig

Owning Collections