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Disruption of paired-associate learning in rat offspring perinatally exposed to dioxins.

Kakeyama M, Endo T, Zhang Y, Miyazaki W, Tohyama C - Arch. Toxicol. (2013)

Bottom Line: The prevalence of cognitive abnormalities in children has partly been ascribed to environmental chemical exposure.Appropriate animal models and tools for evaluating higher brain function are required to examine this problem.Thus, both the chlorinated dioxin and its brominated congener affected higher brain function to a similar extent in a nearly identical manner.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Bunkyo-ku, Tokyo, 113-0033, Japan.

ABSTRACT
The prevalence of cognitive abnormalities in children has partly been ascribed to environmental chemical exposure. Appropriate animal models and tools for evaluating higher brain function are required to examine this problem. A recently developed behavioral test in which rats learn six unique flavor-location pairs in a test arena was used to evaluate paired-associate learning, a hallmark of the higher cognitive function that is essential to language learning in humans. Pregnant Long-Evans rats were dosed by gavage with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) at a dose of 0, 200, or 800 ng/kg (referred as Control, TCDD-200, TCDD-800, TBDD-200, or TBDD-800, hereafter) on gestational day 15, and the offspring was tested during adulthood. Paired-associate learning was found to be impaired in the TCDD-200 and TBDD-200 groups, but not in either group exposed to 800 ng/kg, the observations of which were ensured by non-cued trials. As for the emotional aspect, during habituation, the TCDD-200 and TBDD-200 groups showed significantly longer latencies to enter the test arena from a start box than the Control, TCDD-800, and TBDD-800 groups, suggesting that the TCDD-200 and TBDD-200 groups manifested anxiety-like behavior. Thus, both the chlorinated dioxin and its brominated congener affected higher brain function to a similar extent in a nearly identical manner. Use of the behavioral test that can evaluate paired-associate learning in rats demonstrated that in utero and lactational exposure to not only TCDD but also TBDD perturbed higher brain function in rat offspring in a nonmonotonic manner.

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a The event arena is composed of a test arena [1,600 (w) × 1,600 (d) × 300 (h) mm] with a start box [250 (w) × 250 (d) × 300 (h) mm] at the center of each sidewall. b Arrangement of six flavor-location paired associations (F-L pairs) in the event arena. At each location (1–6), there was a well in which a specific-flavored rat chow (as described in the following parentheses) was concealed under sand. 1 F1-L1 (chocolate); 2 F2-L2 (cherry); 3 F3-L3 (anise); 4 F4-L4 (bacon); 5 F5-L5 (coconut); and 6 F6-L6 (strawberry). Rats were presented with flavored lab chow in the start box as a cue, and they were allowed to recall the spatial location with which it was associated and to go into the arena to search for the rat chow with the identical flavor (Tse et al. 2007)
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Fig1: a The event arena is composed of a test arena [1,600 (w) × 1,600 (d) × 300 (h) mm] with a start box [250 (w) × 250 (d) × 300 (h) mm] at the center of each sidewall. b Arrangement of six flavor-location paired associations (F-L pairs) in the event arena. At each location (1–6), there was a well in which a specific-flavored rat chow (as described in the following parentheses) was concealed under sand. 1 F1-L1 (chocolate); 2 F2-L2 (cherry); 3 F3-L3 (anise); 4 F4-L4 (bacon); 5 F5-L5 (coconut); and 6 F6-L6 (strawberry). Rats were presented with flavored lab chow in the start box as a cue, and they were allowed to recall the spatial location with which it was associated and to go into the arena to search for the rat chow with the identical flavor (Tse et al. 2007)

Mentions: The details of behavioral test of paired-associate learning for rats using the event arena apparatus have been described previously (Tse et al. 2007, 2011). In the event arena, sand wells can be placed at any location among a total of 49 locations on a 7 × 7 grid (Fig. 1a), in which rats have to dig through sand to obtain reward pellets as a reward.Fig. 1


Disruption of paired-associate learning in rat offspring perinatally exposed to dioxins.

Kakeyama M, Endo T, Zhang Y, Miyazaki W, Tohyama C - Arch. Toxicol. (2013)

a The event arena is composed of a test arena [1,600 (w) × 1,600 (d) × 300 (h) mm] with a start box [250 (w) × 250 (d) × 300 (h) mm] at the center of each sidewall. b Arrangement of six flavor-location paired associations (F-L pairs) in the event arena. At each location (1–6), there was a well in which a specific-flavored rat chow (as described in the following parentheses) was concealed under sand. 1 F1-L1 (chocolate); 2 F2-L2 (cherry); 3 F3-L3 (anise); 4 F4-L4 (bacon); 5 F5-L5 (coconut); and 6 F6-L6 (strawberry). Rats were presented with flavored lab chow in the start box as a cue, and they were allowed to recall the spatial location with which it was associated and to go into the arena to search for the rat chow with the identical flavor (Tse et al. 2007)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3927058&req=5

Fig1: a The event arena is composed of a test arena [1,600 (w) × 1,600 (d) × 300 (h) mm] with a start box [250 (w) × 250 (d) × 300 (h) mm] at the center of each sidewall. b Arrangement of six flavor-location paired associations (F-L pairs) in the event arena. At each location (1–6), there was a well in which a specific-flavored rat chow (as described in the following parentheses) was concealed under sand. 1 F1-L1 (chocolate); 2 F2-L2 (cherry); 3 F3-L3 (anise); 4 F4-L4 (bacon); 5 F5-L5 (coconut); and 6 F6-L6 (strawberry). Rats were presented with flavored lab chow in the start box as a cue, and they were allowed to recall the spatial location with which it was associated and to go into the arena to search for the rat chow with the identical flavor (Tse et al. 2007)
Mentions: The details of behavioral test of paired-associate learning for rats using the event arena apparatus have been described previously (Tse et al. 2007, 2011). In the event arena, sand wells can be placed at any location among a total of 49 locations on a 7 × 7 grid (Fig. 1a), in which rats have to dig through sand to obtain reward pellets as a reward.Fig. 1

Bottom Line: The prevalence of cognitive abnormalities in children has partly been ascribed to environmental chemical exposure.Appropriate animal models and tools for evaluating higher brain function are required to examine this problem.Thus, both the chlorinated dioxin and its brominated congener affected higher brain function to a similar extent in a nearly identical manner.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Bunkyo-ku, Tokyo, 113-0033, Japan.

ABSTRACT
The prevalence of cognitive abnormalities in children has partly been ascribed to environmental chemical exposure. Appropriate animal models and tools for evaluating higher brain function are required to examine this problem. A recently developed behavioral test in which rats learn six unique flavor-location pairs in a test arena was used to evaluate paired-associate learning, a hallmark of the higher cognitive function that is essential to language learning in humans. Pregnant Long-Evans rats were dosed by gavage with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) at a dose of 0, 200, or 800 ng/kg (referred as Control, TCDD-200, TCDD-800, TBDD-200, or TBDD-800, hereafter) on gestational day 15, and the offspring was tested during adulthood. Paired-associate learning was found to be impaired in the TCDD-200 and TBDD-200 groups, but not in either group exposed to 800 ng/kg, the observations of which were ensured by non-cued trials. As for the emotional aspect, during habituation, the TCDD-200 and TBDD-200 groups showed significantly longer latencies to enter the test arena from a start box than the Control, TCDD-800, and TBDD-800 groups, suggesting that the TCDD-200 and TBDD-200 groups manifested anxiety-like behavior. Thus, both the chlorinated dioxin and its brominated congener affected higher brain function to a similar extent in a nearly identical manner. Use of the behavioral test that can evaluate paired-associate learning in rats demonstrated that in utero and lactational exposure to not only TCDD but also TBDD perturbed higher brain function in rat offspring in a nonmonotonic manner.

Show MeSH
Related in: MedlinePlus