Behavioral assessments of learning and attention in rats exposed perinatally to 3,3',4,4',5-pentachlorobiphenyl (PCB 126)
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.
Bushnell
P J
PJ
Neurotoxicology Division, United States Environmental Protection Agency, Research Triangle Park, NC 27711, USA. bushnell.philip@epamail.epa.gov
Rice
D C
DC
D000818:Animals; D000831:Animals, Newborn; D001288:Attention / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D002707:Chlordiazepoxide / Q000633:toxicity*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004965:Estrogen Antagonists / Q000633:toxicity; D005074:Evoked Potentials, Visual / Q000187:drug effects; D005260:Female; D018757:GABA Modulators / Q000633:toxicity; D007858:Learning / Q000187:drug effects*; D008297:Male; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans
D004965:Estrogen Antagonists; D018757:GABA Modulators; D002707:Chlordiazepoxide; D011078:Polychlorinated Biphenyls; C023035:3,4,5,3',4'-pentachlorobiphenyl