Discriminative stimulus effects of cocaine and amphetamine in rats following developmental exposure to polychlorinated biphenyls (PCBs)

Abstract

Polychlorinated biphenyls (PCBs) are environmental neurotoxicants known to affect the brain dopaminergic (DA) system. This project investigated whether developmental exposure to PCBs would alter the discriminative stimulus effects of psychostimulant drugs known to act on the DA system. Female Long-Evans rats were orally exposed to 0, 3, or 6 mg/kg/day of an environmentally relevant PCB mixture from four weeks prior to breeding through weaning of their litters on PND 21. When they reached adulthood one male and female/litter were trained to discriminate cocaine (10.0 mg/kg, IP) from saline by repeatedly pairing cocaine injections with reinforcement on one operant response lever, and saline injections with reinforcement on the other lever. After response training, generalization tests to four lower doses of cocaine (7.5, 5.0, 2.5, and 1.25 mg/kg, IP) and to amphetamine (1.0, 0.5, 0.25, and 0.125 mg/kg, IP) were given two days/ week, with additional training dose days in-between. Percent responding of the PCB-exposed rats on the cocaine-paired lever was significantly higher than that of controls for the highest generalization dose of cocaine, and lower than that of controls for the highest dose of amphetamine. Response rate and percent responding on the cocaine lever did not differ among the exposure groups on the days when the training dose of cocaine was given, suggesting the generalization test results were not due to pre-existing differences in discrimination ability or rate of responding. These findings suggest developmental PCB exposure can alter the interoceptive cues of psychostimulants.

A comparison of presynaptic and postsynaptic dopaminergic agonists on inhibitory control performance in rats perinatally exposed to PCBs

“…These findings are in line with our expectations and replicate previous research using the same dosing regimen with the Fox River PCB mixture (Sable et al, 2009; 2010)…”

“…Dosing procedures, including a rationale for the doses selected have previously been explained in detail (Kostyniak et al, 2005; Sable et al 2006; 2009; 2010). Briefly, a stock solution of the Fox River PCB mixture (Kostyniak et al, 2005) was diluted with corn oil to make three dosing solutions: 0 μl/ml PCBs (corn oil only), 7.5 μl/ml PCBs, and 15.0 μl/ml PCBs.…”

“…Physiological measures, including the dam liver weight, dam implantation sites, and brain:body weight, liver:body weight, and thymus:body weight ratios in the pups at the time of weaning, were determined to confirm PCB exposure (see Sable et al, 2010). Other general developmental outcomes, including the percent gestational and lactational weight gain, and postnatal body weights of the pups on PND 0, 7, 14, and 21 were also collected.…”

Cocaine self-administration in male and female rats perinatally exposed to PCBs: Evaluating drug use in an animal model of environmental contaminant exposure.

“…As previously mentioned, differences in cocaine (unpublished results) and amphetamine (Poon et al, 2013) behavioral sensitization and drug discrimination (Sable et al, 2011) have been found in adult rats perinatally exposed to PCBs in comparison to controls. Likewise, other studies using animal models have reported that developmental exposure to lead (Clifford et al, 2011; D.…”

Cocaine sensitization in adult Long-Evans rats perinatally exposed to polychlorinated biphenyls

“…First, alterations in the discriminative stimulus effects of cocaine and amphetamine were observed in adult rats perinatally exposed to PCBs (Sable, Monaikul, Poon, Eubig, & Schantz, 2011). Also, research demonstrated that the locomotor activating effects following a single intraperitoneal amphetamine injection, as well as behavioral sensitization to repeated intraperitoneal injections of amphetamine, were affected by perinatal PCB exposure (Poon, Monaikul, Kostyniak, Chi, Schantz, & Sable, 2013).…”