Postnatal lead exposure induces supersensitivity to the stimulus properties of a D2-D3 agonist

Cory‐Slechta, Deborah A.; Pokora, M. J.; Widzowski, Dan

doi:10.1016/0006-8993(92)90180-h

Cited by 37 publications

(6 citation statements)

References 33 publications

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Section: Discussionsupporting

confidence: 93%

“…Our results are consistent with previous studies of early postnatal insult with agents such as lead, amphetamine, or Mn that reported lasting impacts on the dopaminergic system as well as altered executive function behaviors in adults (McDougall et al,2008; Reichel et al,2006; Cory‐Slechta et al,1992; Decker et al,2005; Nowak et al,2001; Widzowski et al,1994). Cory‐Slechta et al (1992) found that developmental lead exposure in rats led to altered dopamine receptor binding associated with changes in D2 receptor sensitivity in an operant drug discrimination test in adult (PND 60) animals. More recently, Reichel et al (2006) and McDougall et al (2008) exposed rats to Mn levels up to 750 μg Mn/d over PND 1‐21 and observed impaired acquisition of a fixed ratio 1 task, altered amphetamine‐ or cocaine‐induced locomotion, reductions in dopamine transporter levels in the striatum and nucleus accumbens, and a decrease in cocaine‐stimulated dopamine release in the striatum of PND 90 adults, ∼70 days after the end of Mn exposure.…”

Section: Discussionsupporting

confidence: 92%

“…Cory-Slechta et al (1992) found that developmental lead exposure in rats led to altered dopamine receptor binding associated with changes in D2 receptor sensitivity in an operant drug discrimination test in adult (PND 60) animals. More recently, Reichel et al (2006) and McDougall et al (2008) exposed rats to Mn levels up to 750 µg Mn/d over PND 1 – 21 and observed impaired acquisition of a fixed ratio 1 task, altered amphetamine- or cocaine-induced locomotion, reductions in dopamine transporter levels in the striatum and nucleus accumbens, and a decrease in cocaine-stimulated dopamine release in the striatum of PND 90 adults, ~70 days after the end of Mn exposure.…”

Section: Discussionmentioning

confidence: 99%

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Preweaning Mn exposure leads to prolonged astrocyte activation and lasting effects on the dopaminergic system in adult male rats

Kern

Smith

2010

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Little is known about the effects of manganese (Mn) exposure over neurodevelopment and whether these early insults result in effects lasting into adulthood. To determine if early Mn exposure produces lasting neurobehavioral and neurochemical effects, we treated neonate rats with oral Mn (0, 25, or 50 mg Mn/kg/d over PND 1-21) and evaluated 1) behavioral performance in the open arena in the absence (PND 97) and presence (PND 98) of a d-amphetamine challenge, 2) brain dopamine D1 and D2-like receptors and dopamine transporter densities in the prefrontal cortex, striatum, and nucleus accumbens (PND 107), and 3) astrocyte marker glial fibrillary acidic protein (GFAP) levels in these same brain regions (PND 24 and 107). We found that pre-weaning Mn exposure did not alter locomotor activity or behavior disinhibition in adult rats, though Mnexposed animals did exhibit an enhanced locomotor response to d-amphetamine challenge. Preweaning Mn exposure led to increased D1 and D2 receptor levels in the nucleus accumbens and prefrontal cortex, respectively, compared to controls. We also found increased GFAP expression in the prefrontal cortex in Mn-exposed PND 24 weanlings, and increased GFAP levels in prefrontal cortex, medial striatum and nucleus accumbens of adult (PND 107) rats exposed to preweaning Mn, indicating an effect of Mn exposure on astrogliosis that persisted and/or progressed to other brain regions in adult animals. These data show that pre-weaning Mn exposure leads to lasting molecular and functional impacts in multiple brain regions of adult animals, long after brain Mn levels returned to normal.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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Preweaning Mn exposure leads to prolonged astrocyte activation and lasting effects on the dopaminergic system in adult male rats

Kern

Smith

2010

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“…Lead (Pb) toxicity is more common in children and may produce learning disorders and hyperactive behavior (Davis et al, 1990;Needleman et al, 1990). Behavioral and cognitive effects of Pb-exposure have been well documented in developing and adult animals (Cory-Slechta et al, 1992). The nervous system is the primary target for the low levels of Pb-exposure and the developing brain appears to be especially vulnerable to Pb-neurotoxicity (Kuhlmann et al, 1977;Zawia et al, 1998;Reddy and Zawia, 2000;Chetty et al, 2001;Basha et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Lead induced effects on acetylcholinesterase activity in cerebellum and hippocampus of developing rat

Reddy¹,

Basha²,

Devi

et al. 2003

Intl J of Devlp Neuroscience

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Exposure to low-levels of lead (Pb) during early development has been implicated in behavioral abnormalities and cognitive deficits in children. The present study is focused on developmental changes in hippocampus and cerebellum of rats following perinatal exposure to Pb. Pregnant rats were exposed to 0.2% Pb-acetate from gestation day 6 (GD 6) through postnatal day (PND) 21 and the activity levels of acetylcholinesterase (AChE) were estimated in cerebellum and hippocampus of pups at specific time points for 5 weeks. In both the brain regions, Pb-exposure decreased AChE activity with an increase in age. Histochemical observations conducted in 35 days old rat brain showed decreased AChE activity conspicuously in stratum oriens and dentate gyrus of hippocampus, and molecular and granule cell layers of cerebellum. In vitro studies conducted in 35 days old rat brain showed a considerable decrease in the specific activity of AChE at high concentrations (50-100 microM) of Pb in a concentration-dependent manner. However, at low concentrations (5-20 microM), Pb failed to produce such changes. In the presence of eserine (physostigmine), the specific inhibitor of AChE, the inhibitory effect of Pb was potentiated and this was more pronounced at low-concentrations of Pb. The behavioral responses in open-field also showed a significant decrease in both Pb exposed as well as eserine administered rats. These data suggest that low-level perinatal Pb-exposure induces alterations in cholinergic system in the cerebellum and hippocampus of developing brain even after the withdrawal of Pb-exposure, that may contribute to behavioral and learning deficits.

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“…For example, cholinergic antagonism in the 6-8-h posttraining time and D1-mediated dopamine agonism in the 10-12-h period result in loss of learning-associated NCAM polysialylation activation and amnesia at the 24-h recall time (Doyle and Regan, 1993). The lead-induced delays in the learning-associated polysialylation response may be relevant to the dopamine receptor supersensitivity observed in animals with prior postnatal lead exposure (Cory-Slechta and Widzowski, 1991;Cory-Slechta et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Low‐Level Lead Exposure in the Early Postnatal Period Results in Persisting Neuroplastic Deficits Associated with Memory Consolidation

Murphy

Regan

1999

Journal of Neurochemistry

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Prospective studies in humans and experimental investigations in animals have correlated elevated perinatal blood lead levels with enduring behavioural and cognitive perturbations. Although deficits in neuroplastic events necessary for long-term memory consolidation have been observed during the postnatal period, there is little evidence that these persist into adulthood in the absence of continued lead exposure. To address this issue, we exposed Wistar rat pups to 400 mg of PbCI,/L via their dams' drinking water from postnatal day 1 to 30. At postnatal day 80, the animals were trained in a onetrial, step-through, light-dark passive avoidance paradigm. Prior postnatal lead exposure resulted in a significant decline in recall latency on posttraining day 5, an effect that was specific to the learned response as no obvious behavioural alterations were apparent in openfield studies. As recall was unaffected in the immediate 48-h posttraining period, this suggested an enduring impairment in events associated with long-term memory storage. To investigate this further, we determined the influence of prior lead exposure on the transient modulations of hippocampal neural cell adhesion molecule polysialylation state that occur in the 10-12-h posttraining period, a neuroplastic event associated with memory consolidation. Direct quantification of polysialylated dentate neurons revealed prior lead exposure to have no effect on basal number but to significantly delay and blunt the transient increase observed in control animals at the 12-h posttraining time. These findings confirm that lead exposure in the postnatal period results in enduring neuroplastic deficits most likely associated with reordering of connections in pathways subservient to memory consolidation.

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Postnatal lead exposure induces supersensitivity to the stimulus properties of a D2-D3 agonist

Cited by 37 publications

References 33 publications

Preweaning Mn exposure leads to prolonged astrocyte activation and lasting effects on the dopaminergic system in adult male rats

Preweaning Mn exposure leads to prolonged astrocyte activation and lasting effects on the dopaminergic system in adult male rats

Lead induced effects on acetylcholinesterase activity in cerebellum and hippocampus of developing rat

Low‐Level Lead Exposure in the Early Postnatal Period Results in Persisting Neuroplastic Deficits Associated with Memory Consolidation

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