The effects of dopamine agonists on fixed interval schedule-controlled behavior are selectively altered by low-level lead exposure

Cory‐Slechta, Deborah A.; Pokora, M. J.; Preston, Ray A.

doi:10.1016/0892-0362(96)00082-7

Cited by 29 publications

(24 citation statements)

References 21 publications

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“…Developmental exposure to EDCs alone and as a mixture led to multiple behavioral deficiencies in adulthood in behaviors that included a fixed interval reinforcement schedule (FI), novel object recognition (NOR) paradigm and spontaneous locomotor activity, all known to involve mesocorticolimbic mediation (Antunes and Biala, 2012, Cory-Slechta, Pazmino, 1997, Cory-Slechta et al, 1998, Ennaceur et al, 2005, Evans and Cory-Slechta, 2000) predicated on the fact that developmental exposures to these EDCs are known to alter monoaminergic neural pathways (De Coster and van Larebeke, 2012, Frye et al, 2012, Suzuki, Mizuo, 2003), particularly along the mesolimbic dopaminergic systems (Palanza et al 2008). Specifically, behavioral deficits were found in response to all five EDC treatments, but were enhanced with exposure to a mixture of EDCs in a sex-specific manner, with only males showing unique behavioral deficits compared to the single EDC exposed males.…”

Section: Discussionmentioning

confidence: 99%

“…It is interesting to think about the possibility that these results reflect altered underlying mesocorticolimbic dopamine function, as we have previously reported a U-shaped curve relating dopamine to FI response rates (Cory-Slechta, 1998), wherein either increases or decreases in dopamine ultimately suppress FI response rates through their ability to suppress locomotor (low levels) and induce stereotypy (high levels). This will require future assessment of dose effect curves for dopamine-related changes in response to the single EDCs and the mixture.…”

Section: Discussionmentioning

confidence: 99%

“…EDCs have been implicated in the increased incidence of neurobehavioral disorders with sex biased prevalence rates, such as ADHD and autism, where males are increasingly susceptible (Colborn, 2004a, b, Frye, Bo, 2012). Such research will should include the generation of full dose-effect curves for individual EDCs and the MIX, particularly given findings of non-monotonic dose effect curves and the recognition of the non-linearity of underlying neurobiological substrates, e.g., dopamine (Cory-Slechta, 2005, Cory-Slechta, O'Mara, 1998, Evans and Cory-Slechta, 2000). Further, the fundamental role of sex hormones in behavioral neurodevelopment, including time-course assessments of hormone profiles will be requisite to this understanding.…”

Section: Discussionmentioning

confidence: 99%

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Sex-specific enhanced behavioral toxicity induced by maternal exposure to a mixture of low dose endocrine-disrupting chemicals

et al. 2014

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Humans are increasingly and consistently exposed to a variety of endocrine disrupting chemicals (EDCs), chemicals that have been linked to neurobehavioral disorders such as ADHD and autism. Many of such EDCs have been shown to adversely influence brain mesocorticolimbic systems raising the potential for cumulative toxicity. As such, understanding the effects of developmental exposure to mixtures of EDCs is critical to public health protection. Consequently, this study compared the effects of a mixture of four EDCs to their effects alone to examine potential for enhanced toxicity, using behavioral domains and paradigms known to be mediated by mesocorticolimbic circuits (Fixed Interval (FI) schedule controlled behavior, novel object recognition memory and locomotor activity) in offspring of pregnant mice that had been exposed to vehicle or relatively low doses of four EDCs, Atrazine (ATR – 10mg/kg), Perfluorooctanoic acid (PFOA – 0.1 mg/kg), Bisphenol-A (BPA - 50μg/kg), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD – 0.25μg/kg) alone or combined in a mixture (MIX), from gestational day 7 until weaning. EDC-treated males maintained significantly higher horizontal activity levels across 3 testing sessions, indicative of delayed habituation, whereas no effects were found in females. Statistically significant effects of MIX were seen in males, but not females, in the form of increased FI response rates, in contrast to reductions in response rate with ATR, BPA and TCDD, and reduced short term memory in the novel object recognition paradigm. MIX also reversed the typically lower neophobia levels of males compared to females. With respect to individual EDCs, TCDD produced notable increases in FI response rates in females, and PFOA significantly increased ambulatory locomotor activity in males. Collectively, these findings show the potential for enhanced behavioral effects of EDC mixtures in males and underscore the need for animal studies to more fully investigate mixtures, including chemicals that converge on common physiological substrates to examine potential mechanisms of toxicity with full dose effect curves to assist in interpretations of relevant mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Sex-specific enhanced behavioral toxicity induced by maternal exposure to a mixture of low dose endocrine-disrupting chemicals

et al. 2014

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“…(Bemis and Seegal, 1999, 2000; Stewart et al 2003a). In regard to the first question, we specifically predicted that postnatal Pb would predict impaired performance because a large volume of animal literature relating Pb to impulsive operant responding is found with postnatal exposures (Brockel and Cory-Slechta 1998; Cory-Slechta 1990; Cory-Slechta et al 1996, 1998). We are not aware of any literature of comparable volume that relates prenatal Pb to impulsive responding on operant schedules.…”

Section: Discussionmentioning

confidence: 99%

Response Inhibition During Differential Reinforcement of Low Rates (DRL) Schedules May Be Sensitive to Low-Level Polychlorinated Biphenyl, Methylmercury, and Lead Exposure in Children

Stewart

Sargent

Reihman

et al. 2006

Environ Health Perspect

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BackgroundAnimal studies have shown that exposure to common, low-level environmental contaminants [e.g., polychlorinated biphenyls (PCBs), lead] causes excessive and inappropriate responding on intermittent reinforcement schedules. The Differential Reinforcement of Low Rates task (DRL) has been shown to be especially sensitive to low-level PCB exposure in monkeys.ObjectivesWe investigated the relationships between prenatal PCB and postnatal Pb exposure performance on a DRL schedule in children. We predicted that a) prenatal PCB exposure would reduce interresponse times (IRTs) and reinforcements earned, and b) postnatal Pb exposure would reduce IRTs and reinforcements earned.MethodsWe tested 167 children on a DRL20 (20 sec) reinforcement schedule, and recorded IRTs and the number of reinforced responses across the session. We measured prenatal PCB exposure (cord blood), methylmercury (MeHg) (maternal hair), and postnatal Pb exposure (venous blood), and > 50 potentially confounding variables.ResultsResults indicated impaired performance in children exposed to PCBs, MeHg, and Pb. Children prenatally exposed to PCBs responded excessively, with significantly lower IRTs and fewer reinforcers earned across the session. In addition, exposure to either MeHg or Pb predicted statistically significant impairments of a similar magnitude to those for PCBs, and the associated impairments of all three contaminants (PCB, MeHg, and Pb) were statistically independent of one another.ConclusionsThese results, taken with animal literature, argue the high sensitivity of DRL performance to low-level PCB, MeHg, and Pb exposure. Future research should employ behavioral tasks in children, such as DRL, that have been demonstrably sensitive to low-level PCB, MeHg, and Pb exposure in animals.

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“…For example, some studies have found that lead exposure produces a particular vulnerability of mesolimbic DA systems and this can result in motor behavior alterations (Zuch et al, 1998;Cory-Slechta et al, 1998). Moreover, ex vivo and in vitro studies indicated that inorganic lead is distributed, among other nuclei, in the striatum and cerebral cortex (Moreira et al, 2001;Ramesh et al, 2001).…”

Section: Introductionmentioning

confidence: 96%

Motor behavior and brain enzymatic changes after acute lead intoxication on different strains of mice

2004

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The effects of dopamine agonists on fixed interval schedule-controlled behavior are selectively altered by low-level lead exposure

Cited by 29 publications

References 21 publications

Sex-specific enhanced behavioral toxicity induced by maternal exposure to a mixture of low dose endocrine-disrupting chemicals

Sex-specific enhanced behavioral toxicity induced by maternal exposure to a mixture of low dose endocrine-disrupting chemicals

Response Inhibition During Differential Reinforcement of Low Rates (DRL) Schedules May Be Sensitive to Low-Level Polychlorinated Biphenyl, Methylmercury, and Lead Exposure in Children

Motor behavior and brain enzymatic changes after acute lead intoxication on different strains of mice

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