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 Miquel

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4455-4467
Number of pages13
JournalPsychopharmacology
Volume232
Issue number24
DOIs
StatePublished - 1 Dec 2015

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Cocaine
Cerebellum
Injections
Purkinje Cells
Brain-Derived Neurotrophic Factor
Locomotion
Basal Ganglia
Pharmaceutical Preparations
Synapses
Extracellular Matrix
Research

Keywords

  • BDNF
  • Cerebellum
  • Cocaine
  • GluR2
  • Sensitisation
  • Withdrawal

Cite this

Vazquez-Sanroman, D., Carbo-Gas, M., Leto, K., Cerezo-Garcia, M., Gil-Miravet, I., Sanchis-Segura, C., ... Miquel, M. (2015). Cocaine-induced plasticity in the cerebellum of sensitised mice. Psychopharmacology, 232(24), 4455-4467. https://doi.org/10.1007/s00213-015-4072-1
Vazquez-Sanroman, Dolores ; Carbo-Gas, Maria ; Leto, Ketty ; Cerezo-Garcia, Miguel ; Gil-Miravet, Isis ; Sanchis-Segura, Carla ; Carulli, Daniela ; Rossi, Ferdinando ; Miquel, Marta. / Cocaine-induced plasticity in the cerebellum of sensitised mice. In: Psychopharmacology. 2015 ; Vol. 232, No. 24. pp. 4455-4467.
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Vazquez-Sanroman, D, Carbo-Gas, M, Leto, K, Cerezo-Garcia, M, Gil-Miravet, I, Sanchis-Segura, C, Carulli, D, Rossi, F & Miquel, M 2015, 'Cocaine-induced plasticity in the cerebellum of sensitised mice', Psychopharmacology, vol. 232, no. 24, pp. 4455-4467. https://doi.org/10.1007/s00213-015-4072-1

Cocaine-induced plasticity in the cerebellum of sensitised mice. / Vazquez-Sanroman, Dolores; Carbo-Gas, Maria; Leto, Ketty; Cerezo-Garcia, Miguel; Gil-Miravet, Isis; Sanchis-Segura, Carla; Carulli, Daniela; Rossi, Ferdinando; Miquel, Marta.

In: Psychopharmacology, Vol. 232, No. 24, 01.12.2015, p. 4455-4467.

Research output: Contribution to journalArticle

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T1 - Cocaine-induced plasticity in the cerebellum of sensitised mice

AU - Vazquez-Sanroman, Dolores

AU - Carbo-Gas, Maria

AU - Leto, Ketty

AU - Cerezo-Garcia, Miguel

AU - Gil-Miravet, Isis

AU - Sanchis-Segura, Carla

AU - Carulli, Daniela

AU - Rossi, Ferdinando

AU - Miquel, Marta

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Y1 - 2015/12/1

N2 - 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.

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Vazquez-Sanroman D, Carbo-Gas M, Leto K, Cerezo-Garcia M, Gil-Miravet I, Sanchis-Segura C et al. Cocaine-induced plasticity in the cerebellum of sensitised mice. Psychopharmacology. 2015 Dec 1;232(24):4455-4467. https://doi.org/10.1007/s00213-015-4072-1