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Effects of successive intrastriatal methylmercury administrations on dopaminergic system
L R F Faro1, R Durán, J L M Do Nascimento
1Departamento de Fisiologia, Centro de Ciências Biológicas, UFPA, PA, Belém, Brazil.
Abstract:
The present study was carried out in order to determine the effects of intrastriatal administration of different doses (40 microM, 400 microM, and 4mM) of methylmercury (MeHg) on dopaminergic system of rat striatum. Experiments were performed in conscious and freely moving rats using brain microdialysis coupled with liquid chromatography. Intrastriatal administration of MeHg produced significant increases in dopamine (DA) striatal levels (907+/-7%, 1870+/-319%, and 7971+/-534% for the doses of 40, 400 microM, and 4mM, with respect to basal). The increase in DA levels was associated with significant decreases in extracellular levels of its main metabolites dihydroxyphenylacetic acid (DOPAC) and homovallinic acid (HVA) (65.0+/-3.0% and 52.2+/-1.3%, respectively) using the dose of 4mM MeHg, whereas nonsignificant changes in metabolite levels were observed with the doses of 40 and 400 microM MeHg. A second infusion of 4mM MeHg 24h after first infusion also produced a rise of DA levels, but this increase was very small as compared with that produced by first infusion (7971+/-534% versus 985+/-186%). This second infusion of 4mM MeHg also decreased DOPAC and HVA levels, but this decrease was not significant as compared with that observed after first infusion (65.0+/-3.0% and 52.2+/-1.3% versus 62.4+/-5.2% and 63.4+/-7.4%, respectively). We discuss these effects based on a stimulated DA release and/or a decreased DA intraneuronal degradation.
Insights
Methylmercury (MeHg) significantly increases dopamine (DA) levels in rat striatum, while decreasing its metabolites. Repeated MeHg exposure shows a diminished DA release response.
Area of Science:
- Neuroscience
- Toxicology
Background:
- Methylmercury (MeHg) is a potent neurotoxin.
- The dopaminergic system is crucial for motor control and reward pathways.
- Understanding MeHg's impact on dopamine is vital for neuroprotection strategies.
Purpose of the Study:
- To investigate the dose-dependent effects of intrastriatal methylmercury (MeHg) on the dopaminergic system in rat striatum.
- To analyze changes in dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovallinic acid (HVA).
Main Methods:
- Intrastriatal administration of varying methylmercury (MeHg) doses (40 microM, 400 microM, 4mM) in conscious, freely moving rats.
- Brain microdialysis coupled with liquid chromatography to measure extracellular dopamine and its metabolites.
- Repeated dose administration to assess tolerance development.
Main Results:
- MeHg caused significant, dose-dependent increases in striatal dopamine (DA) levels.
- A high dose (4mM) of MeHg led to significant decreases in DOPAC and HVA, indicating altered dopamine metabolism.
- A second MeHg infusion 24 hours later resulted in a markedly reduced DA release and non-significant decreases in metabolites, suggesting tolerance.
Conclusions:
- Intrastriatal methylmercury (MeHg) disrupts dopaminergic neurotransmission by increasing dopamine release and altering its metabolism.
- The observed tolerance to repeated MeHg administration suggests adaptive mechanisms within the dopaminergic system.
- These findings provide insights into the neurotoxic mechanisms of MeHg and potential therapeutic targets.