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The cerebellum on cocaine: plasticity and metaplasticity
Author(s) -
VazquezSanroman Dolores,
Leto Ketty,
CerezoGarcia Miguel,
CarboGas María,
SanchisSegura Carla,
Carulli Daniela,
Rossi Ferdinando,
Miquel Marta
Publication year - 2015
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12223
Subject(s) - neuroscience , cerebellum , purkinje cell , subiculum , ampa receptor , synaptic plasticity , neuroplasticity , biology , chemistry , hippocampal formation , receptor , medicine , glutamate receptor , dentate gyrus
Despite the fact that several data have supported the involvement of the cerebellum in the functional alterations observed after prolonged cocaine use, this brain structure has been traditionally ignored and excluded from the circuitry affected by addictive drugs. In the present study, we investigated the effects of a chronic cocaine treatment on molecular and structural plasticity in the cerebellum, including BDNF , D 3 dopamine receptors, Δ FosB , the G lu2 AMPA receptor subunit, structural modifications in P urkinje neurons and, finally, the evaluation of perineuronal nets ( PNN s) in the projection neurons of the medial nucleus, the output of the cerebellar vermis. In the current experimental conditions in which repeated cocaine treatment was followed by a 1‐week withdrawal period and a new cocaine challenge, our results showed that cocaine induced a large increase in cerebellar pro BDNF levels and its expression in P urkinje neurons, with the mature BDNF expression remaining unchanged. Together with this, cocaine‐treated mice exhibited a substantial enhancement of D 3 receptor levels. Both Δ FosB and AMPA receptor G lu2 subunit expressions were enhanced in cocaine‐treated animals. Significant pruning in P urkinje dendrite arborization and reduction in the size and density of P urkinje boutons contacting deep cerebellar projection neurons accompanied cocaine‐dependent increase in pro BDNF . Cocaine‐associated effects point to the inhibitory P urkinje function impairment, as was evidenced by lower activity in these cells. Moreover, the probability of any remodelling in P urkinje synapses appears to be decreased due to an upregulation of extracellular matrix components in the PNN s surrounding the medial nuclear neurons.