Behavioral assessments of learning and attention in rats exposed perinatally to 3,3',4,4',5-pentachlorobiphenyl (PCB 126) 1999

P J Bushnell, and D C Rice
Neurotoxicology Division, United States Environmental Protection Agency, Research Triangle Park, NC 27711, USA. bushnell.philip@epamail.epa.gov

Evidence from humans suggests that cognitive dysfunction may result from perinatal exposure to polychlorinated biphenyls (PCBs), and the results of some animal research with PCBs have been interpreted in terms of possible impairment of attention. Long-Evans rats were fed 3,3',4,4',5-pentachlorobiphenyl (PCB 126), a coplanar congener, at doses of 0.25 or 1 microgram/kg/day [corrected] throughout gestation and nursing. Male offspring of these rats were trained as adults to perform 2 tests of attention for food reward. First, a cued target-detection task, modeled after Posner's covert orienting method for humans, was used to assess visuospatial attention. In this task, a visual target stimulus was presented in 1 visual hemifield on each trial, preceded either by a valid cue, an invalid cue, or no cue. A valid cue appeared in the same hemifield as the target, and an invalid cue appeared in the opposite hemifield. As expected, valid cues increased accuracy and speed of target detection and invalid cues decreased accuracy and speed; moreover, these effects were systematically related to changes in cue intensity and target duration. However, perinatal exposure to PCB 126 did not affect acquisition or performance of this task. The second task assessed sustained attention by means of a signal detection method in which a brief, spatially-constant but temporally unpredictable, visual signal indicated which of 2 responses would yield food. Varying the intensity of the signal greatly affected the probability of correctly reporting the signal. Perinatal exposure to PCB 126 did not affect acquisition of the response rule or performance of the task. Finally, all rats were challenged with chlordiazepoxide (CDP) at doses of 0, 3, 5, 8, or 12 mg/kg SC, 20 min before testing in the sustained attention task. In control rats, low doses (3, 5, and 8 mg/kg) of CDP reduced accuracy at low signal intensities only, suggesting an increase in visual threshold. The high dose of CDP reduced accuracy at all signal intensities and increased the false-alarm rate as well, suggesting an impairment of attention. The rats exposed perinatally to PCB 126 at 0.25 micrograms/kg [corrected] were unaffected by CDP, and those exposed to PCB 126 at 1 microgram/kg [corrected] showed a smaller decrement in performance after CDP than did the controls. Taken together, these data provide little support for the possibility that perinatal exposure to PCB 126 causes deficits in attention, but suggest that PCB 126 may alter GABA-mediated pathways in the CNS during development.

UI MeSH Term Description Entries
D007858 Learning Relatively permanent change in behavior that is the result of past experience or practice. The concept includes the acquisition of knowledge. Phenomenography
D008297 Male Males
D011078 Polychlorinated Biphenyls Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants. PCBs,Polychlorinated Biphenyl,Polychlorobiphenyl Compounds,Biphenyl, Polychlorinated,Biphenyls, Polychlorinated,Compounds, Polychlorobiphenyl
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D002707 Chlordiazepoxide An anxiolytic benzodiazepine derivative with anticonvulsant, sedative, and amnesic properties. It has also been used in the symptomatic treatment of alcohol withdrawal. Methaminodiazepoxide,7-Chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine-4-oxide,7-Chloro-N-methyl-5-phenyl-3H-1,4-benzodiazepin-2-amine 4-oxide,Chlordiazepoxide Hydrobromide,Chlordiazepoxide Hydrochloride,Chlordiazepoxide Monohydrochloride,Chlordiazepoxide Perchlorate,Chlozepid,Elenium,Librium,7 Chloro 2 methylamino 5 phenyl 3H 1,4 benzodiazepine 4 oxide,7 Chloro N methyl 5 phenyl 3H 1,4 benzodiazepin 2 amine 4 oxide,Hydrobromide, Chlordiazepoxide,Hydrochloride, Chlordiazepoxide,Monohydrochloride, Chlordiazepoxide,Perchlorate, Chlordiazepoxide
D003463 Cues Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. Cue
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D004965 Estrogen Antagonists Compounds which inhibit or antagonize the action or biosynthesis of estrogenic compounds. Estradiol Antagonists,Antagonists, Estradiol,Antagonists, Estrogen
D005074 Evoked Potentials, Visual The electric response evoked in the cerebral cortex by visual stimulation or stimulation of the visual pathways. Visual Evoked Response,Evoked Potential, Visual,Evoked Response, Visual,Evoked Responses, Visual,Potential, Visual Evoked,Potentials, Visual Evoked,Response, Visual Evoked,Responses, Visual Evoked,Visual Evoked Potential,Visual Evoked Potentials,Visual Evoked Responses

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