Developmental exposure to PCBs and/or MeHg: Effects on a differential reinforcement of low rates (DRL) operant task before and after amphetamine drug challenge

Abstract

The current study assessed the effects of developmental PCB and/or MeHg exposure on an operant task of timing and inhibitory control and determined if amphetamine (AMPH) drug challenges differentially affected performance. Long-Evans rats were exposed to corn oil (control), PCBs alone (1 or 3 mg/kg), MeHg alone (1.5 or 4.5 ppm), the low combination (1 mg/kg PCBs + 1.5 ppm MeHg), or the high combination (3 mg/kg PCBs + 4.5 ppm MeHg) throughout gestation and lactation. An environmentally relevant, formulated PCB mixture was used. Male and female offspring were trained to asymptotic performance on a differential reinforcement of low rates (DRL) operant task as adults. PCB-exposed groups had a lower ratio of reinforced to non-reinforced responses than controls. Groups exposed to MeHg alone were not impaired and the deficits observed in PCB-exposed groups were not seen when PCBs were co-administered with MeHg. AMPH was less disruptive to responding in males receiving PCBs alone, MeHg alone, and 1.0 mg/kg PCB + 1.5 ppm MeHg. Paradoxically, the disruption in responding by AMPH in males given 3.0 mg/kg PCB + 4.5 ppm MeHg did not differ from controls. Exposed females from all treatment groups did not differ from controls in their AMPH response. Overall, the findings suggest that developmental exposure to PCBs can decrease DRL performance. Co-exposure to MeHg seemed to mitigate the detrimental effects of PCBs on performance. The finding that the disruptive effects of AMPH on DRL performance were lessened in some groups of exposed males suggests that alterations in dopaminergic functioning may have a role in behavioral changes seen after perinatal PCB and MeHg exposure.

Strategy set-shifting and response inhibition in adult rats exposed to an environmental polychlorinated biphenyl mixture during adolescence

“…Some animal studies have reported sex-specific effects in rats exposed to PCBs. For instance, a previous study done in our lab found deficits on DRL15 performance in response to amphetamine following perinatal PCB exposure, and this effect seemed to be driven by poorer performance in males (Sable et al, 2009). The authors hypothesized that this sex difference may be due to PCB-induced reductions in aromatase activity (Hany et al, 1999), an enzyme responsible for the conversion of testosterone to estradiol, which may influence proper sexual differentiation of the brain as well as the proper development of the dopaminergic system in the prefrontal cortex of the developing male rat (Stewart & Rajabi, 1994).…”

“…In one study using DRL15, rats exposed perinatally to the Fox River PCB mixture showed a lower ratio of reinforced to non-reinforced responses suggesting an impairment on this task (Sable et al, 2009). However, an earlier study found no significant effect of perinatal PCB treatment on DRL15 performance, although PCB-exposed rats did not extinguish lever pressing as readily as controls when tested on an extinction phase (Sable et al, 2006).…”

“…However, an earlier study found no significant effect of perinatal PCB treatment on DRL15 performance, although PCB-exposed rats did not extinguish lever pressing as readily as controls when tested on an extinction phase (Sable et al, 2006). These studies used the same PCB mixture and doses; however, an important difference between these two studies was that the rats that showed a deficit in performance were only tested on the DRL task (Sable et al , 2009), whereas in the study that did not see an effect of exposure rats were tested on a different operant task prior to DRL testing (Sable et al , 2006). Thus, it is possible that a transfer of experience occurred such that rats exposed to another operant task prior to DRL testing tended to perform the task more efficiently than rats for which the DRL task was their first exposure to operant training.…”

“…These doses used in previous perinatal exposure studies were physiologically relevant because offspring born to dams given these doses appear phenotypically similar to children born to mothers with moderate to high PCB body burdens (Fein et al, 1984; Stewart et al, 2006). In particular, at these doses offspring have been shown to weigh less than control pups at birth and at weaning (Kostyniak et al , 2005) and have shown deficits in inhibitory control (Sable et al, 2009). Thus, as this study was the first to use this mixture in adolescent rats, we chose these dose levels that have had effects on cognition and behavior after perinatal exposure as a starting point to explore our hypotheses.…”

“…In particular, deficits in cognitive flexibility have been seen in rats and monkeys perinatally exposed to PCBs (reviewed in Sable & Schantz, 2006). Response inhibition is also disrupted in rats (Sable et al, 2009), monkeys (Rice & Hayward, 1997; Rice, 1998) and children (Stewart et al, 2006) developmentally exposed to PCBs.…”