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Developmental Exposure to Cocaine Dynamically Dysregulates Cortical Arc/Arg3.1 Modulation in Response to a Challenge

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Abstract

During adolescence, the medial prefrontal cortex (mPFC) is still developing. We have previously shown that developmental cocaine exposure alters mPFC’s ability to cope with challenging events. In this manuscript, we exposed rats developmentally treated with cocaine to a novelty task and analyzed the molecular changes of mPFC. Rats were exposed to cocaine from post-natal day (PND) 28 to PND 42 and sacrificed at PND 43, immediately after the novel object recognition (NOR) test. Cocaine-treated rats spent more time exploring the novel object than saline-treated counterparts, suggesting an increased response to novelty. The messenger RNA (mRNA) and protein levels of the immediate early gene Arc/Arg3.1 were reduced in both infralimbic (IL) and prelimbic (PL) cortices highlighting a baseline reduction of mPFC neuronal activity as a consequence of developmental exposure to cocaine. Intriguingly, significant molecular changes were observed in the IL, but not PL, cortex in response to the combination of cocaine exposure and test such as a marked upregulation of both Arc/Arg3.1 mRNA and protein levels only in cocaine-treated rats. As for proteins, such increase was observed only in the post-synaptic density and not in the whole homogenate, suggesting psychostimulant-induced changes in trafficking of Arc/Arg3.1 or an increased local translation. Notably, the same profile of Arc/Arg3.1 was observed for post-synaptic density (PSD)-95 leading to the possibility that Arc/Arg3.1 and PSD-95 bridge together to promote aberrant synaptic connectivity in IL cortex following repeated exposure to cocaine during brain development.

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Acknowledgements

We would like to thank the Zardi Gori Foundation for funding this project through a grant to FF.

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Authors and Affiliations

  1. Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy

    Lucia Caffino, Giuseppe Giannotti, Francesca Mottarlini, Giorgio Racagni & Fabio Fumagalli

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  1. Lucia Caffino
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  2. Giuseppe Giannotti
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  3. Francesca Mottarlini
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  4. Giorgio Racagni
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  5. Fabio Fumagalli
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Corresponding author

Correspondence to Fabio Fumagalli.

Ethics declarations

Procedures involving animals and their care were conducted in conformity with institutional guidelines that are in compliance with national (D.L. n. 116, G.U., supplement 40, 18 Febbraio, 1992, Circolare No. 8, G.U., 14 Luglio, 1994) and international laws and policies (EEC Council Directive 2010/63/UE; Guide for the Care and Use of Laboratory Animals, National Academies Press, 8th Edition, 2011)

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The authors declare that they have no conflict of interest

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Caffino, L., Giannotti, G., Mottarlini, F. et al. Developmental Exposure to Cocaine Dynamically Dysregulates Cortical Arc/Arg3.1 Modulation in Response to a Challenge. Neurotox Res 31, 289–297 (2017). https://doi.org/10.1007/s12640-016-9683-8

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  • DOI: https://doi.org/10.1007/s12640-016-9683-8

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