Abstract
Cyclohexane (CHX) is an organic solvent commonly used as a drug-of-abuse. This drug increases the oxidative stress and glial reactivity in the hippocampus, which suggests that this brain region is vulnerable to CHX effects. This study aimed to establish the behavioral changes and the pathological alterations that occur in the Cornu Ammonis 3 (CA3) and Dentate Gyrus (DG) after a long-lasting exposure to CHX. We exposed CD1 mice to a recreational-like dose of CHX (~ 30,000 ppm) for 30 days and explored its consequences in motor skills, reward-seeking behavior, and the CA3 and DG hippocampal subfields. Twenty-four hours after the last administration of CHX, we found a significant decrease in the number of c-Fos+ cells in the hippocampal CA3 and DG regions. This event coincided with an increased in NMDAR1 expression and apoptotic cells in the CA3 region. At day 13th without CHX, we found a persistent reduction in the number of c-Fos+ and TUNEL+ cells in DG. At both time points, the CHX-exposed mice showed a strong overexpression of neuropeptide Y (NPY) in the CA3 stratum lucidum and the hippocampal hilus. In parallel, we used an operant-based task to assess motor performance and operant conditioning learning. The behavioral analysis indicated that CHX did not modify the acquisition of operant conditioning tasks, but affected some motor skills and increased the reward-seeking behavior. Altogether, this evidence reveals that CHX exposure provokes long-lasting changes in the hippocampal subfields, induces motor impairments and increases the motivation-guided behavior. These findings can help understand the deleterious effect of CHX into the adult hippocampus and unveil its potential to trigger addiction-like behaviors.
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This work was supported by grants from the Consejo Nacional de Ciencia y Tecnologia (CONACyT No. PN 2015-01-465 and INFR-280414) and the Programa para el Desarrollo Profesional Docente PRODEP (213544) for OGP, and the CONACyT Fellowship Grants for TCO and DZL (No. 736339 and No. 738774). JB was supported by a Grant from CONACyT INFR-281265.
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TCO conception and design of experiments, data collection, analysis, interpretation and manuscript writing. DZL data collection, analysis, and interpretation. NIC data collection, analysis and interpretation. JB design of behavioral experiments, data collection and analysis, and financial support. OGP design and conception of the study, data interpretation, manuscript writing, financial support and final approval of the manuscript.
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Campos-Ordonez, T., Zarate-Lopez, D., Ibarra-Castaneda, N. et al. Cyclohexane Inhalation Produces Long-Lasting Alterations in the Hippocampal Integrity and Reward-Seeking Behavior in the Adult Mouse. Cell Mol Neurobiol 39, 435–449 (2019). https://doi.org/10.1007/s10571-019-00660-0
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DOI: https://doi.org/10.1007/s10571-019-00660-0