Abstract
Rationale
Cocaine base paste (CBP) is an illegal drug of abuse usually consumed by adolescents in a socio-economically vulnerable situation. Repeated drug use targets key brain circuits disrupting the processes that underlie emotions and cognition. At the basis of such neuroadaptations lie changes in the expression of immediate-early genes (IEGs). Nevertheless, changes in transcriptional regulation associated with CBP consumption remain unknown.
Objectives
We aimed to describe behavioral phenotype related to locomotion, anxiety-like behavior, and memory of CBP-injected mice and to study IEGs expression after an abstinence period.
Methods
Five-week-old female CF-1 mice were i.p. injected daily with vehicle or CBP (40 mg/kg) for 10 days and subjected to a 10-day period of abstinence. Open field and novel object recognition tests were used to evaluate locomotion and anxiety-like behaviors and recognition memory, respectively, during chronic administration and after abstinence. After abstinence, prefrontal cortex (mPFC) and nucleus accumbens (NAc) were isolated and gene expression analysis performed through real-time PCR.
Results
We found an increase in locomotion and anxiety-like behavior during CBP administration and after the abstinence period. Furthermore, the CBP group showed impaired recognition memory after abstinence. Egr1, FosB, ΔFosB, Arc, Bdnf, and TrkB expression was upregulated in CBP-injected mice in NAc and FosB, ΔFosB, Arc, and Npas4 expression was downregulated in mPFC. We generated an anxiety score and found positive and negative correlations with IEGs expression in NAc and mPFC, respectively.
Conclusion
Our results suggest that chronic CBP exposure induced alterations in anxiety-like behavior and recognition memory. These changes were accompanied by altered IEGs expression.
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Acknowledgments
We are grateful to Secretaría de Programación para la Prevención de la Drogadicción (SEDRONAR, Argentina) for supplying CBP seized samples. We would also like to thank the staff at the Bioterio Central, Facultad de Ciencias Exactas y Naturales, UBA, for their assistance with mice.
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The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Agencia Nacional de Promoción Científica y Tecnológica, Argentina (Grant PICT-2013-0653), and Universidad de Buenos Aires (Grant UBACYT20020130100011).
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Authors BB, EF, and LB undertook all behavioral and biochemical studies and assisted in the interpretation of the results. OG designed the statistical analysis and prepared the figures and tables. EC initiated and designed the study, collected and analyzed the experimental results, and wrote the final draft of the manuscript. NP provided critical revision of the manuscript. BB and NP contributed to the final manuscript. All the authors read and approved the final version of the manuscript for submission.
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Experiments were performed in accordance with local regulations and the National Institutes of Health (NIH) Guide of the Care and Use of Laboratory Animals (NIH publication 80-23/96) and were previously approved by the Ethical Committee (CICUAL) of the Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (Protocol No 0054/16).
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Berardino, B.G., Fesser, E.A., Belluscio, L.M. et al. Effects of cocaine base paste on anxiety-like behavior and immediate-early gene expression in nucleus accumbens and medial prefrontal cortex of female mice. Psychopharmacology 236, 3525–3539 (2019). https://doi.org/10.1007/s00213-019-05321-0
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DOI: https://doi.org/10.1007/s00213-019-05321-0