Effect of subchronic exposure to ambient fine and ultrafine particles on rat motor activity and ex vivo striatal dopaminergic transmission

Abstract

Alterations in dopaminergic transmission are associated with neurological disorders, such as depression, autism, and Parkinson’s disease. Exposure of rats to ambient fine (FP) or ultrafine (UFP) particles induces oxidative and inflammatory responses in the striatum, a neuronal nucleus with dense dopaminergic innervation and critically involved in the control of motor activity.

Objectives: We used an ex vivo system to evaluate the effect of in vivo inhalation exposure to FP and UFP on motor activity and dopaminergic transmission.

Materials and Methods: Male adult Wistar rats were exposed to FP, UFP, or filtered air for 8 weeks (subchronic exposure; 5 h/day, 5 days/week) in a particle concentrator. Motor activity was evaluated using the open-field test. Uptake and release of [³H]-dopamine were assessed in striatal synaptosomes, and dopamine D₂ receptor (D₂R) affinity for dopamine was evaluated by the displacement of [³H]-spiperone binding to striatal membranes.

Results: Exposure to FP or UFP significantly reduced spontaneous motor activity (ambulatory distance: FP −25%, UFP −32%; ambulatory time: FP −24%, UFP −22%; ambulatory episodes: FP −22%, UFP −30%), decreased [³H]-dopamine uptake (FP −18%, UFP −24%), and increased, although not significantly, [³H]-dopamine release (113.3 ± 16.3 and 138.6 ± 17.3%). Neither FP nor UFP exposure affected D₂R density or affinity for dopamine.

Conclusions: These results indicate that exposure to ambient particulate matter reduces locomotion in rats, which could be related to altered striatal dopaminergic transmission: UFP was more potent than FP. Our results contribute to the evidence linking environmental factors to changes in brain function that could turn into neurological and psychiatric disorders.

HIGHLIGHTS

• Young adult rats were exposed to fine (FP) or ultrafine (UFP) particles for 40 days.

• Exposure to FP or UFP reduced motor activity.

• Exposure to FP or UFP reduced dopamine uptake by striatal synaptosomes.

• Neither D₂R density or affinity for dopamine was affected by FP or UFP.

• UFP was more potent than FP to exert the effects reported.

Keywords:

• Fine particles
• ultrafine particles
• dopamine
• D₂ receptor
• motor activity
• striatum
• air pollution

Acknowledgments

We acknowledge the excellent technical assistance of Marisela Uribe-Ramírez, Gerardo Martinez-Aguilar, Y. Margarita Martínez Domínguez, and Raúl González-Pantoja.

Author contributions

M.A.A.O., J.A.A.M., and A.D.V.R designed the study. M.A.A.O., G.E.M.F., Y.D.G., and J.E.S. performed the experiments. M.A.A.O., J.A.A.M., and A.D.V.R performed data analysis. B.F. contributed experimental resources. O.A.M. performed organic compound analysis. R.D.G. performed elemental analysis. M.A.A.O., J.A.A.M., and A.D.V.R. wrote the manuscript. M.K. participated in data analysis and reviewed and edited the manuscript. All authors revised and approved the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

M.A.A.O. held a Conacyt graduate scholarship (281111). This work was supported by Cinvestav (Proyecto 166 SEP-Cinvestav to J.-A.A.M.) and Conacyt (grants 220448 to J.-A.A.M. and 167778 and 286739 to A.D.V.R.). The funding sources were not involved at all in the study design, collection, analysis, and interpretation of data, writing of the manuscript, or the decision to submit this report.