Brief Postnatal PBDE Exposure Alters Learning and the Cholinergic Modulation of Attention in Rats

Abstract

Polybrominated diphenyl ethers (PBDEs), chemicals commonly used as flame retardants, are ubiquitous in the environment and bioaccumulate in humans and wildlife. However, little is known about their potential toxicological properties. In the present study, male Long-Evans rats orally administered the commercial PBDE mixture DE-71 or corn oil for 1 week, beginning at postnatal day (PND) 6, were tested on a visual discrimination task and two sustained attention tasks. After completion of these tasks, the rats were administered a drug challenge with the muscarinic antagonist scopolamine (0, 0.01, 0.03, 0.05 mg/kg), which was injected subcutaneously 30 min prior to testing on the second sustained attention task. The DE-71-exposed rats demonstrated deficits in learning but not in sustained attention when compared to controls. Scopolamine impaired the animals' ability to detect the brief visual cues in controls, as evidenced by decreases in accuracy and increases in omission errors. However, the DE-71-exposed rats were subsensitive to the effects of scopolamine on omission errors, particularly on trials in which a long delay preceded the cue, suggesting alterations in the cholinergic modulation of sustained attention. For the DE-71-exposed rats, the lack of sustained attention deficits in the absence of the drug, coupled with the subsensitivity to scopolamine's effects on sustained attention, suggest that although this PBDE mixture produced lasting alterations in cholinergic functioning, either (1) these alterations were not of sufficient magnitude to be behaviorally relevant, or (2) behavioral deficits resulting from these alterations were overcome by the development of compensatory neural mechanisms or response strategies in adulthood.

The developmental neurotoxicity of polybrominated diphenyl ethers: Effect of DE‐71 on dopamine in zebrafish larvae

“…This result is in agreement with in vitro data obtained using cultured rat striatal synaptosomes exposed to PBDE, which found decreased DA in the synaptosomes [11], and an in vivo study in mice showing that DE-71 exposure caused a significant decrease in striatal DA and DOPAC [12]. It has also been shown that other environmental contaminants such as PCBs can affect dopaminergic signaling [29].…”

“…All rights reserved neurotransmitter system [10], and have neurotoxic effects on DA homeostasis, glutamatergic neurotransmission, and locomotor behavior [11,12]. In this regard, dopaminergic neurons are particularly interesting because they are known to play a critical role in motor control, cognition, motivation, and reward associated behavior, as well as endocrine regulation [13,14].…”

Developmental neurotoxicity of polybrominated diphenyl ether (PBDE) flame retardants

“…Starting on PND 30, animals were tested in a visual discrimination learning task, in which they performed significantly worse than controls. In contrast, DE-71 did not alter sustained attention or inhibitory control, though treated animals were sub-sensitive to the effect of the cholinergic muscarinic antagonist scopolamine on attention (Dufault et al 2005). Finally, in a study (presented, however, only in abstract form) in which DE-71 was given to rats from GD 6 to PND 21 at the doses of 5, 30 and 100 mg/kg, tests of fear conditioning revealed a dose-dependent decrease in cue-but not context-based performance in male offspring tested as adults (Taylor et al 2003).…”

“…In another postnatal exposure study, Long-Evans rats were given the pentaBDE mixture DE-71 by gavage from PND 6 to 12 (Dufault et al 2005). Starting on PND 30, animals were tested in a visual discrimination learning task, in which they performed significantly worse than controls.…”

PBDE flame retardants

“…However, PBDE neurotoxicity has been observed absent impacts on TH regulation, suggesting other mechanistic pathways. Indeed, a growing body of evidence suggests that PBDE mechanisms of neurotoxicity may operate by several pathways that include disrupted TH signaling, altered cholinergic neurotransmissions 215,216 ; impaired neuronal proliferation and plasticity, 191,214,217 and oxidative stress. 218,219 While the underlying mechanisms of PBDE neurotoxicity are unclear, continued testing in fish would be informative to better understand these underlying mechanisms of PBDEs effects on the development and functioning of the central and peripheral nervous systems of vertebrates.…”