Working memory in bisphenol-A treated middle-aged ovariectomized rats

Abstract

Over 90% of the U.S. population has detectable bisphenol-A (BPA) in their urine according to recent biomonitoring data. BPA is best known for its estrogenic properties, and most rodent research on the nervous system effects of BPA has focused on determining if chronic exposures during pre- and perinatal development have organizational effects on brain development and behavior. Estrogens also have important impacts on brain and behavior during adulthood, particularly in females during aging, but the impact of BPA on the adult brain is less studied. We have published a series of studies documenting that chronic exposure to various estrogens including 17β-estradiol, ERβ selective SERMs and soy phytoestrogens impairs performance of middle-aged female rats on an operant working memory task. The purpose of this study was to determine if chronic oral exposure to BPA would alter working memory on this same task. Ovariectomized (OVX) middle-aged Long Evans rats were tested on an operant delayed spatial alternation (DSA) task. Rats were treated for 8-10 weeks with either a 0 (vehicle control), 5 or 50 μg/kg bw/day oral bolus of BPA. A subset of the vehicle control rats was implanted with a Silastic implant containing 17β-estradiol (low physiological range) to serve as a positive control. All rats were tested for 25 sessions on the DSA task. BPA treatment did not influence performance accuracy on the DSA task, whereas 17β-estradiol significantly impaired performance, as previously reported. The results of this study suggest that chronic oral exposure to BPA does not alter working memory processes of middle-aged OVX rats assessed by this operant DSA task.

Figure 1

Treatment and testing schedule for BPA and vehicle dosing.

Figure 2

Multiple comparison results of proportion correct during NCA training (Mean ± SEM). The estradiol treated group performed worse than did the BPA50, BPA5 and oil treated groups,* p<0.05.

Figure 3

(A–E). Multiple comparison results of proportion correct across five 5-session blocks of testing, sorted by intertrial delay (Mean ± SEM). * The estradiol treated group performed worse than did all treatment groups (p<0.05). ** The estradiol treated group performed worse than did the oil treated group (p<0.05). *** The estradiol treated group performed worse than did the BPA5 treated group (p<0.05). **** The estradiol treated group performed worse than did the BPA 50 treated group (p<0.05).

Figure 4

Multiple comparison results of error patterns (Mean ± SEM). (A) Win-stay errors committed across five 5-session blocks of DSA testing. The estradiol treated group committed more errors than did the BPA5 and oil treated groups, *p<0.05. (B) Total lose-stay errors committed on the DSA task across 25 sessions of testing. The estradiol treated group committed more errors overall than did the other three treatment groups, *p<0.05.

Figure 5

ANOVA results of lever press latencies (Mean ± SEM). (A) Latency to lever press following a correct response across five 5-session blocks of DSA testing. No differences were measured between treatment groups, p>0.05. (B) Latency to lever press following an incorrect response across five 5-session blocks of DSA testing. No differences were measured between treatment groups, p>0.05.