Altered profiles of spontaneous novelty seeking, impulsive behavior, and response to D-amphetamine in rats perinatally exposed to bisphenol A.

Abstract

Bisphenol A (BPA) is an environmental estrogen with potentially averse effects on public health. We studied the long-term effects of perinatal exposure to BPA on later behavior in adult rats of both sexes. BPA or vehicle was administered orally to mother rats from mating to pups' weaning, at a concentration (0.040 mg/kg) within the range of human exposure. The offspring of both sexes were tested at adolescence (postnatal days 35-45) for novelty preference (experiment 1). After a 3-day familiarization to one side of a two-chamber apparatus, on day 4 rats were allowed to freely explore the whole apparatus. BPA-exposed females spent significantly less time than did controls in exploration of the novel side (i.e., increased neophobia), whereas no effect was found in the male group. At adulthood, the same animals were food deprived and tested for profiles of impulsive behavior (experiment 2), in operant chambers provided with two nose-poking holes (delivering either five or one food pellet). After the establishment of a baseline preference for the large reinforcer, a delay was introduced before the delivery of the five food pellets, which was progressively increased each day (10, 20, 30, 45, 60, 80, 100 sec). As expected, all animals exhibited a progressive shift toward the immediate but smaller reinforcer. A reduced level of impulsive behavior (i.e., a shift to the right in the intolerance-delay curve) was evidenced in BPA-treated rats. The frequency of inadequate responding (during the length of the delay) also provided a measure of restless behavior. Interestingly, the profile of BPA-treated males was feminized, strongly resembling that of control females. Animals were then tested (experiment 3) for the response to an amphetamine challenge (1 mg/kg, subcutaneously). The drug-induced increment activity was significantly less marked in BPA-treated male rats compared with controls. These findings provide clear indirect evidence of long-term alterations in brain monoaminergic function after perinatal BPA exposure. This may be a cause for concern for public health, confirming that exposure to a weak environmental estrogen in the period of sexual differentiation of the brain can influence adult behavior.

Home cage testing of delay discounting in rats

“…Interestingly, instead of showing an exclusive preference (i.e., 100% for LL), they occasionally chose the alternative SS possibility. This finding, which replicated those of previous experiments in our lab (Adriani, Caprioli, et al, 2003;Adriani, Della Seta, et al, 2003;Adriani & Laviola, 2006;Adriani et al, 2004), indicates that animals express a constant and active patrolling over the two alternative possibilities, as they adaptively probe whether there is any change over time in the outcome associated with nose poking at the nonpreferred hole.…”

“…In summary, the present ID task was run in tight agreement with previous experiments at our lab (Adriani, Caprioli, Granstrem, Carli, & Laviola, 2003;Adriani, Della Seta, Dessì-Fulgheri, Farabollini, & Laviola, 2003;Adriani & Laviola, 2006;Adriani et al, 2004), with a few minimal changes: First, the TO was elevated to 90 sec; second, the system was active daily during two sessions of 1 h each, rather than during 25-min sessions once daily. These changes allowed an overall reduction in the total duration of the schedule (i.e., only 9 days) and were indeed possible due to the fact that the panel was provided inside the home cage of the subject, rather than in dedicated operant chambers.…”

“…Similar results have been found in previous studies (cf. Adriani, Caprioli, et al, 2003;Adriani, Della Seta, et al, 2003;Adriani & Laviola, 2006). To be able to compare the present results with those in previous studies, it is necessary to recalculate the outcomes with respect to TO duration.…”

Temporal Effects of Bisphenol A on Dopaminergic Neurons: An Experiment on Adult Rats

“…Since animals are very sensitive to exogenous chemicals during perinatal or neonatal periods, many animal studies have focused on these times. The effects of perinatal exposure to bisphenol A have been shown to affect various aspects of behavior such as exploratory, sociosexual [22], and aggressive behaviors [23], as well as anxiety levels [24], and nociception [25], and the response to D-amphetamine [26]. Impairment by bisphenol A of sexual differentiation of exploratory behavior and the size of the locus coeruleus was also observed [27], and it also increased depression-like behavior [28].…”

Comparative Study on Toxicokinetics of Bisphenol A in F344 Rats, Monkeys (Macaca fascicularis), and Chimpanzees (Pan troglodytes)

“…It is possible that humans might also absorb BPA more easily than experimental rats. Both behavioral and neurological alterations in rodents by perinatal low-dose BPA exposure per os even at < 100 µg/kg/day [1] would strongly suggest potential adverse effects of chronic environmental exposure to BPA in humans (< 10 µg/kg/day), if the differences in bioavailability between rodents and primates including humans also applies to much lower dose exposure to BPA. We conclude that there are considerable differences in distribution, metabolism, and excretion of BPA between rodents and primates.…”