Spatial reversal learning in Aroclor 1254-exposed rats: sex-specific deficits in associative ability and inhibitory control.
Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that have been associated with cognitive deficits in children exposed in utero. Cognitive deficits due to PCB exposure have also been documented in animal models, but the underlying behavioral mechanisms responsible for those deficits remain to be elucidated. The current study examined the effects of gestational and lactational exposure to PCBs on spatial discrimination-reversal learning (spatial RL) in rats using standard two-lever operant testing chambers. Pregnant Long-Evans rats (10/dose) received either 0 or 6 mg/kg Aroclor 1254 (A1254) po in corn oil from gestational day 6 to postnatal day 21. One male and one female from each litter were tested on spatial RL beginning at 190-220 days of age. Animals were reinforced with a 45-mg food pellet for pressing the lever associated with the correct spatial location (either left or right). After reaching 85% correct performance for 2 consecutive days, the opposite spatial location was reinforced. Five of these position reversals were given. Male rats exposed to A1254 made significantly more total errors (121.6 +/- 12.5) on the first reversal than controls (90.7 +/- 5.8). In contrast, female rats exposed to A1254 exhibited deficits on the fourth and fifth reversals (23.6 +/- 4.2, 17.0 +/- 2.8 and 36.7 +/- 4.7, 26.8 +/- 2.5 for control and exposed animals, respectively). Response-pattern analyses in the A1254-exposed male and female rats revealed fundamental differences in the underlying behavioral mechanisms responsible for the deficits. A1254-exposed males exhibited an increased tendency to incorrectly respond to the previously correct stimulus (i.e., perseverate) following a reversal while A1254-exposed females exhibited impairments in their ability to make new associations with a reinforced spatial location (i.e., associative deficit). These data provide new insights into the underlying behavioral mechanisms that may be responsible for the spatial learning deficits observed in PCB-exposed rodents and monkeys.
Widholm
J J
JJ
Department of Veterinary Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802, USA. jwidholm@uiuc.edu
Clarkson
G B
GB
Strupp
B J
BJ
Crofton
K M
KM
Seegal
R F
RF
Schantz
S L
SL
D000704:Analysis of Variance; D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D020111:Chlorodiphenyl (54% Chlorine) / Q000494:pharmacology*; D005260:Female; D007858:Learning / Q000187:drug effects*; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D012727:Sex Characteristics; D013037:Spatial Behavior / Q000187:drug effects*
D013956:Antithyroid Agents; D020111:Chlorodiphenyl (54% Chlorine)