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A single cocaine exposure disrupts actin dynamics in the cortico-accumbal pathway of adolescent rats: modulation by a second cocaine injection

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Abstract

Rationale and objectives

Among the changes caused by repeated exposure to drugs of abuse, structural rearrangements play a critical role, setting the stage for maladaptive responses to environmental challenges and sustaining drug-taking and drug-seeking behaviors. Given that adolescents are more vulnerable to drug abuse than adults and based on our recent data showing that a single exposure to cocaine during adolescence is sufficient to change the adolescent brain, we decided to investigate whether acute cocaine exposure may alter actin remodeling in reward-related brain regions.

Methods

Accordingly, we decided to evaluate if F-actin/G-actin ratio was altered by a single injection of cocaine (20 mg/kg) at postnatal day 35. We also evaluated whether the first administration of cocaine influences such a ratio in response to a second injection (10 mg/kg) provided 24 h or 7 days later.

Results

Within the medial prefrontal cortex, a single cocaine injection increases the F-actin/G-actin ratio. This effect lasts 1 week, and it is not affected by the second injection of cocaine, indicating a persistent effect of the first exposure. In the nucleus accumbens, cocaine reduces the F-actin/G-actin ratio 24 h later. Seven days later, instead, such a ratio is markedly increased: notably, the additional exposure to the psychostimulant normalizes the F-actin/G-actin ratio.

Conclusions

These results suggest that a single cocaine injection during adolescence causes possible changes in actin dynamics and influences the response to a second challenge of the psychostimulant, indicating that early cocaine priming might affect mechanisms regulating synaptic structural plasticity in specific brain regions

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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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Correspondence to Fabio Fumagalli.

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Caffino, L., Giannotti, G., Racagni, G. et al. A single cocaine exposure disrupts actin dynamics in the cortico-accumbal pathway of adolescent rats: modulation by a second cocaine injection. Psychopharmacology 234, 1217–1222 (2017). https://doi.org/10.1007/s00213-017-4559-z

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  • DOI: https://doi.org/10.1007/s00213-017-4559-z

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