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Psychopharmacology

, Volume 232, Issue 24, pp 4455–4467 | Cite as

Cocaine-induced plasticity in the cerebellum of sensitised mice

  • Dolores Vazquez-Sanroman
  • Maria Carbo-Gas
  • Ketty Leto
  • Miguel Cerezo-Garcia
  • Isis Gil-Miravet
  • Carla Sanchis-Segura
  • Daniela Carulli
  • Ferdinando Rossi
  • Marta MiquelEmail author
Original Investigation

Abstract

Rationale

Prior research has accumulated a substantial amount of evidence on the ability of cocaine to produce short- and long-lasting molecular and structural plasticity in the corticostriatal-limbic circuitry. However, traditionally, the cerebellum has not been included in the addiction circuitry, even though growing evidence supports its involvement in the behavioural changes observed after repeated drug experiences.

Objectives

In the present study, we explored the ability of seven cocaine administrations to alter plasticity in the cerebellar vermis.

Methods

After six cocaine injections, one injection every 48 h, mice remained undisturbed for 1 month in their home cages. Following this withdrawal period, they received a new cocaine injection of a lower dose. Locomotion, behavioural stereotypes and several molecular and structural cerebellar parameters were evaluated.

Results

Cerebellar proBDNF and mature BDNF levels were both enhanced by cocaine. The high BDNF expression was associated with dendritic sprouting and increased terminal size in Purkinje neurons. Additionally, we found a reduction in extracellular matrix components that might facilitate the subsequent remodelling of Purkinje-nuclear neuron synapses.

Conclusions

Although speculative, it is possible that these cocaine-dependent cerebellar changes were incubated during withdrawal and manifested by the last drug injection. Importantly, the present findings indicate that cocaine is able to promote plasticity modifications in the cerebellum of sensitised animals similar to those in the basal ganglia.

Keywords

Cerebellum Cocaine Sensitisation Withdrawal BDNF GluR2 

Notes

Acknowledgments

This work was supported by grants and fellowships: Ministerio de Economía y Competitividad [PSI2011- 29181], FPI-PREDOC2009/05, FPU12/04059, PPF 2013 (13I087.01/1) and UJI (P1.1B2011-42).

Conflict of interest

The authors of the present manuscript declare no conflict of interest.

Supplementary material

213_2015_4072_MOESM1_ESM.doc (606 kb)
ESM 1 (DOC 606 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Dolores Vazquez-Sanroman
    • 1
    • 5
  • Maria Carbo-Gas
    • 1
  • Ketty Leto
    • 2
    • 3
  • Miguel Cerezo-Garcia
    • 4
  • Isis Gil-Miravet
    • 1
  • Carla Sanchis-Segura
    • 1
  • Daniela Carulli
    • 2
    • 3
  • Ferdinando Rossi
    • 2
    • 3
  • Marta Miquel
    • 1
    Email author
  1. 1.PsychobiologyUniversitat Jaume ICastellon de la PlanaSpain
  2. 2.Department of Neuroscience, Neuroscience Institute of Turin (NIT)University of TurinTurinItaly
  3. 3.Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (NICO)University of TurinTurinItaly
  4. 4.Plant Physiology Section, Department of CAMNUniversitat Jaume ICastellon de la PlanaSpain
  5. 5.Department of Psychology, Biomedical/Biological Sciences Research Building (BBSR)University of KentuckyLexingtonUSA

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