Postnatal manganese exposure attenuates cocaine-induced locomotor activity and reduces dopamine transporters in adult male rats

Reichel, Carmela M.; Wacan, Jennifer J.; Farley, Cristal M.; Stanley, Brett J.; Crawford, Cynthia A.; McDougall, Sanders A.

doi:10.1016/j.ntt.2006.02.002

Cited by 41 publications

(70 citation statements)

References 69 publications

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“…Mn-induced reductions in DAT protein expression, while modest, were apparent in both the striatum and nucleus accumbens. The latter finding is consistent with previous work from our laboratory showing that DAT binding site density (B max ) in the striatum declined after postnatal Mn exposure (Reichel et al, 2006). Experimental manipulations do not always affect DAT binding sites and protein expression in an identical manner (see Zhu et al, 2005;Shepard et al, 2006), but it now appears that Mn toxicity causes a general reduction in DAT that is detectable using either immunoblotting or radioligand techniques.…”

Section: Discussionsupporting

confidence: 90%

“…Using [ 3 H]GBR 12935, we previously showed that exposing rats to Mn (750 μg) on PD 1-21 reduced the number of striatal DAT binding sites when measured in adulthood (Reichel et al, 2006). One of the goals of the present study was to extend these findings and determine whether postnatal exposure to a high dose of Mn would attenuate DAT protein expression, [ 3 H]dopamine uptake, and dopamine efflux in the striatum and nucleus accumbens of adult rats.…”

Section: Introductionmentioning

confidence: 80%

“…In rats, infusion of Mn during microdialysis reduces K + -stimulated dopamine efflux in the striatum (Vidal et al, 2005), while chronic Mn exposure causes longterm reductions in striatal dopamine levels (Gianutosos and Murray, 1982;Komura and Sakamoto, 1992;Ingersoll et al, 1995;Tran et al, 2002a,b;Aschner et al, 2005). Changes to membrane-associated proteins are also a component of Mn toxicity, because prolonged Mn exposure substantially reduces dopamine transporter (DAT) binding sites in rat and monkey striatum (Eriksson et al, 1992;Reichel et al, 2006). Curiously, studies examining DAT functioning have provided mixed results, with Mn exposure reported to either increase or decrease [ 3 H]-dopamine uptake in rat striatum depending on experimental conditions Leung et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

“…(Golub et al, 2005). In adult rats, unlearned locomotor responding is often disrupted by perturbations of the nigrostriatal and mesocorticolimbic dopamine systems, therefore it is surprising that Mn has been reported to increase (Nachtman et al, 1986;Calabresi et al, 2001), decrease (Ingersoll et al, 1995;Talavera et al, 1999), or have no effect (Dorman et al, 2000;Reichel et al, 2006) on spontaneous locomotor activity. Interestingly, Mn-exposed rats show reduced locomotor responsiveness when challenged with cocaine or amphetamine (indirect dopamine agonists), suggesting that subtle motoric deficits can be unmasked by pharmacological challenge Reichel et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…In adult rats, unlearned locomotor responding is often disrupted by perturbations of the nigrostriatal and mesocorticolimbic dopamine systems, therefore it is surprising that Mn has been reported to increase (Nachtman et al, 1986;Calabresi et al, 2001), decrease (Ingersoll et al, 1995;Talavera et al, 1999), or have no effect (Dorman et al, 2000;Reichel et al, 2006) on spontaneous locomotor activity. Interestingly, Mn-exposed rats show reduced locomotor responsiveness when challenged with cocaine or amphetamine (indirect dopamine agonists), suggesting that subtle motoric deficits can be unmasked by pharmacological challenge Reichel et al, 2006). In the only studies examining whether Mn exposure disrupts learned behaviors, Tran and colleagues found that Mn-and vehicle-treated rats performed similarly on passive avoidance and burrowing detour tasks (Tran et al, 2002b), while Mntreated rats exhibited deficits on a shock avoidance task (Tran et al, 2002a).…”

Section: Introductionmentioning

confidence: 99%

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Postnatal manganese exposure alters dopamine transporter function in adult rats: Potential impact on nonassociative and associative processes

McDougall¹,

Reichel²,

Farley³

et al. 2008

Neuroscience

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In the present study, we examined whether exposing rats to a high-dose regimen of manganese chloride (Mn) during the postnatal period would depress presynaptic dopamine functioning and alter nonassociative and associative behaviors. To this end, rats were given oral supplements of Mn (750 μg/day) on postnatal days (PD) 1-21. On PD 90, dopamine transporter (DAT) immunoreactivity and [ 3 H]dopamine uptake were assayed in the striatum and nucleus accumbens, while in vivo microdialysis was used to measure dopamine efflux in the same brain regions. The effects of postnatal Mn exposure on nigrostriatal functioning were evaluated by assessing rotorod performance and amphetamine-induced stereotypy in adulthood. In terms of associative processes, both cocaineinduced conditioned place preference (CPP) and sucrose-reinforced operant responding were examined. Results showed that postnatal Mn exposure caused persistent declines in DAT protein expression and [ 3 H]dopamine uptake in the striatum and nucleus accumbens, as well as long-term reductions in striatal dopamine efflux. Rotorod performance did not differ according to exposure condition, however Mn-exposed rats did exhibit substantially more amphetamine-induced stereotypy than vehicle controls. Mn exposure did not alter performance on any aspect of the CPP task (preference, extinction, or reinstatement testing), nor did Mn affect progressive ratio responding (a measure of motivation). Interestingly, acquisition of a fixed ratio task was impaired in Mn-exposed rats, suggesting a deficit in procedural learning. In sum, these results indicate that postnatal Mn exposure causes persistent declines in various indices of presynaptic dopaminergic functioning. Mninduced alterations in striatal functioning may have long-term impact on associative and nonassociative behavior.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Postnatal manganese exposure alters dopamine transporter function in adult rats: Potential impact on nonassociative and associative processes

McDougall¹,

Reichel²,

Farley³

et al. 2008

Neuroscience

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Manganese and Rhenium

Santonen¹,

Sainio²

2023

Patty's Toxicology

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Manganese (Mn) and rhenium (Re) are group 7 (VIIB) transition elements. They both can exist in multiple valence states ranging from −3 to +7. While manganese is one of the most abundant elements in the earth's crust, rhenium is one of the rarest elements. The main use of manganese is in steel production. Organic manganese compound methylcyclopentadienyl manganese tricarbonyl (MMT) is used as an additive to gasoline. Rhenium is one of the densest metals known. It is used in high‐temperature superalloys and, for example, in platinum–rhenium catalysts. Manganese is an essential nutrient and readily available from a wide variety of foods. The main target organ of manganese toxicity is the brain. Clinical adverse effects have been described in occupational settings due to inhalation of Mn fumes and dusts, but excessive manganese intake may also result from dietary, environmental, or from its dysfunctional excretion. High exposure to manganese in miners and smelters has led to manganism, that is, a severe movement disorder, cognitive dysfunction, behavioral disturbances, and loss of libido. This is due to manganese accumulation and adverse effects in the brain basal ganglia. Recognition of subtle neurobehavioral effects in workers exposed to lower levels of manganese has led to progressive actions to limit occupational exposure. Manganese exposure has shown also effects in the respiratory system, which, however, may rather be due to particulate matter than to manganese ion. High doses of manganese have affected the sperm parameters and fertility of males in animal studies. Developmental neurotoxicity studies in animals suggest that early Mn exposure may impair learning, memory, and attention of the offspring. Very few information exists on the toxicity of rhenium. Limited evidence suggests low acute toxicity of perrhenates. Perrhenates accumulate in the thyroid. Repeated exposure to ammonium perrhenate has resulted in thyroid enlargement and follicular cell hypertrophy in animals at high doses.

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Manganese and Rhenium

Santonen¹,

Aitio²

2012

Patty's Toxicology

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Manganese is chemically reactive metal with physical characteristics varying from hard and brittle to soft and flexible. Main use of manganese is in steel production. The major non‐metallurgical use of manganese is as manganese dioxide for producing dry‐cell batteries. Organic manganese compounds include methylcyclopentadienyl manganese tricarbonyl used as an additive to gasoline, ethylene‐bis‐dithiocarbamate pesticides maneb and mancozeb, and an image enhancer manganese dipyridoxyl diphosphate. Main health hazard of manganese is neurotoxicity. Recent epidemiological studies show that subtle neurobehavioral effects, including fine deficits in motor performance and in attention, can be seen at exposure levels of ≥0.02–0.03 mg Mn/m 3 as respirable dust. Rhenium is characterized by a very high melting temperature and density. Very few data exist on the toxicity of rhenium.

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Postnatal manganese exposure attenuates cocaine-induced locomotor activity and reduces dopamine transporters in adult male rats

Cited by 41 publications

References 69 publications

Postnatal manganese exposure alters dopamine transporter function in adult rats: Potential impact on nonassociative and associative processes

Postnatal manganese exposure alters dopamine transporter function in adult rats: Potential impact on nonassociative and associative processes

Manganese and Rhenium

Manganese and Rhenium

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