The effects of methylmercury on endogenous dopamine efflux from mouse striatal slices

Kalisch, Bettina E.; Racz, William J.

doi:10.1016/s0378-4274(96)03787-3

Cited by 16 publications

(17 citation statements)

References 26 publications

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“…This study is part of a larger project to determine the neurologic (i.e., behavioral and neurochemical) effects of developmental exposure of laboratory rodents to the toxicants present in Great Lakes salmon. Although the concentrations of PCBs and MeHg used in these experiments are higher then those seen in Great Lakes fish (PCB content ranged from 0.84 to 1.9 ppm, whereas mercury concentrations were 0.34 ppm) (5,6), the concentrations of these contaminants are similar to, or lower than, those used in other in vivo and in vitro studies (18)(19)(20)(21). Furthermore, some human populations consume contaminated pilot whale meat that contains PCB concentrations as high as 30 ppm and mercury levels in the range of 3.3 ppm (22), well within our range of doses.…”

Section: Discussionmentioning

confidence: 60%

Polychlorinated Biphenyls and Methylmercury Act Synergistically to Reduce Rat Brain Dopamine Content in Vitro

Bemis¹,

Seegal²

1999

Environmental Health Perspectives

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Consumption of contaminated Great 1Las fish by pregnant women is associated with decreased birth weight and deficits in cognitive function in their infants and children. These fish contain many known and suspected anthropogenic neurotoxicants, makdig it difficult to determine which contaminant(s) are responsible for the observed deficits. We have undertaken a series of experiments to determine the relevant toxicants by comparing the neurotouic efifect of two of these contaminants-polychorinated biphenyls (PCBs) and metylmercury (MeHg)-both of which are recognized neurotoxicants. Striatal punches obtained from adult rat brain were exposed to PCBs only, MeHg only, or the two in combination, and tissue and media concentrations of dopamine (DA) and its metabolites were determined by high performance liquid chromatography. Exposure to PCBs only reduced tissue DA and elevated media DA in a dose-dependent fashion. Exposure to MeHg only did not significantly affect either measure. However, when striatal punches were simultaneously exposed to PCBs and MeHg, there were significantly greater decreases in tissue DA concentrations and elevations in media DA than those caused by PCBs only, in the absence of changs in media lacte dehydrogenase concentrations. Elevations in both tissue and media 3,4-dihydroxyphenylacetic acid concentrations were also observed. We suggest that the significant interactions between these two toxicants may be due to a common site of action (i.e., toxicant-induced increases in intracellular calcium and changes in second messenger systems) that influences DA function. The synergism between these contamiants suggets that future revisions of fish-consumption guidelines should consider contaminat interactions. Key wordk. dopamine, methyimercury, polychlorinated biphenyls, rat brain, striatal slice, synergism.

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Section: Discussionmentioning

confidence: 60%

Polychlorinated Biphenyls and Methylmercury Act Synergistically to Reduce Rat Brain Dopamine Content in Vitro

Bemis¹,

Seegal²

1999

Environmental Health Perspectives

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“…Both in vivo and in vitro exposure to MeHg alters DA function. Using a mouse striatal slice preparation similar to the one used here, MeHg exposure, at concentrations considerably higher than we used (i.e., 50 pM), resulted in significantly elevated media DA concentrations (20). Similarly, when adult rats were exposed intraperitoneally to MeHg at concentrations ranging from 0.1 to 2 mg/day (for a total dose of 4 or 6 mg), DA concentrations in striatal dialysates obtained by in vivo microdialysis were significantly elevated (21).…”

Section: Methodsmentioning

confidence: 99%

Polychlorinated biphenyls and methylmercury act synergistically to reduce rat brain dopamine content in vitro.

Bemis

Seegal

1999

Environ Health Perspect

136

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“…Dopamine in the prefrontal cortex (PFC) has been shown to be critical for tasks of executive function including inhibitory control (Chudasama and Robbins 2006; Dalley et al 2004; de Bruin et al 2000; Robbins 2000; van der Meulen et al 2007), and both PCB (Fonnum et al 2006; Goodwill et al 2007; Lyng et al 2007) and MeHg (Faro et al 2007; Kalisch and Racz 1996; McKay et al 1986; Minnema et al 1989) exposure have been reported to decrease brain dopamine (DA) levels in rats. These findings provide a potential neurochemical mechanism for the previously described behavioral results and also provide more evidence for the likelihood that PCBs and MeHg may have interactive effects.…”

Section: Introductionmentioning

confidence: 99%

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

Sable

Eubig

Powers

et al. 2009

Neurotoxicology and Teratology

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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.

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The effects of methylmercury on endogenous dopamine efflux from mouse striatal slices

Cited by 16 publications

References 26 publications

Polychlorinated Biphenyls and Methylmercury Act Synergistically to Reduce Rat Brain Dopamine Content in Vitro

Polychlorinated Biphenyls and Methylmercury Act Synergistically to Reduce Rat Brain Dopamine Content in Vitro

Polychlorinated biphenyls and methylmercury act synergistically to reduce rat brain dopamine content in vitro.

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

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