Cocaine-induced plasticity in the cerebellum of sensitised mice.
BACKGROUND
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.


OBJECTIVE
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.
Psychobiology, Universitat Jaume I, Avenida Sos Baynat s/n., 12071, Castellon de la Plana, Spain.|Department of Psychology, Biomedical/Biological Sciences Research Building (BBSR), University of Kentucky, Lexington, KY, USA.
Dolores
D
Vazquez-Sanroman
Psychobiology, Universitat Jaume I, Avenida Sos Baynat s/n., 12071, Castellon de la Plana, Spain.
Maria
M
Carbo-Gas
Department of Neuroscience, Neuroscience Institute of Turin (NIT), University of Turin, Turin, Italy.|Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (NICO), University of Turin, Turin, Italy.
Ketty
K
Leto
Plant Physiology Section, Department of CAMN, Universitat Jaume I, 12071, Castellon de la Plana, Spain.
Miguel
M
Cerezo-Garcia
Psychobiology, Universitat Jaume I, Avenida Sos Baynat s/n., 12071, Castellon de la Plana, Spain.
Isis
I
Gil-Miravet
Psychobiology, Universitat Jaume I, Avenida Sos Baynat s/n., 12071, Castellon de la Plana, Spain.
Carla
C
Sanchis-Segura
Department of Neuroscience, Neuroscience Institute of Turin (NIT), University of Turin, Turin, Italy.|Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (NICO), University of Turin, Turin, Italy.
Daniela
D
Carulli
Department of Neuroscience, Neuroscience Institute of Turin (NIT), University of Turin, Turin, Italy.|Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (NICO), University of Turin, Turin, Italy.
Ferdinando
F
Rossi
Psychobiology, Universitat Jaume I, Avenida Sos Baynat s/n., 12071, Castellon de la Plana, Spain. miquel@uji.es.
Marta
M
Miquel
D000818:Animals; D016739:Behavior, Addictive / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage*; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009473:Neuronal Plasticity / Q000187:drug effects*; D011498:Protein Precursors / Q000378:metabolism; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D000697:Central Nervous System Stimulants; D011498:Protein Precursors; C426674:brain-derived neurotrophic factor precursor; D003042:Cocaine
BDNF; Cerebellum; Cocaine; GluR2; Sensitisation; Withdrawal