Dolores Vazquez-Sanroman1,2, Maria Carbo-Gas1, Ketty Leto3,4, Miguel Cerezo-Garcia5, Isis Gil-Miravet1, Carla Sanchis-Segura1, Daniela Carulli3,4, Ferdinando Rossi3,4, Marta Miquel6. 1. Psychobiology, Universitat Jaume I, Avenida Sos Baynat s/n., 12071, Castellon de la Plana, Spain. 2. Department of Psychology, Biomedical/Biological Sciences Research Building (BBSR), University of Kentucky, Lexington, KY, USA. 3. Department of Neuroscience, Neuroscience Institute of Turin (NIT), University of Turin, Turin, Italy. 4. Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (NICO), University of Turin, Turin, Italy. 5. Plant Physiology Section, Department of CAMN, Universitat Jaume I, 12071, Castellon de la Plana, Spain. 6. Psychobiology, Universitat Jaume I, Avenida Sos Baynat s/n., 12071, Castellon de la Plana, Spain. miquel@uji.es.
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.
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.
Authors: Megan Slaker; Lynn Churchill; Ryan P Todd; Jordan M Blacktop; Damian G Zuloaga; Jacob Raber; Rebecca A Darling; Travis E Brown; Barbara A Sorg Journal: J Neurosci Date: 2015-03-11 Impact factor: 6.167
Authors: Barbara A Sorg; Sabina Berretta; Jordan M Blacktop; James W Fawcett; Hiroshi Kitagawa; Jessica C F Kwok; Marta Miquel Journal: J Neurosci Date: 2016-11-09 Impact factor: 6.167
Authors: V Javier Traver; Filiberto Pla; Marta Miquel; Maria Carbo-Gas; Isis Gil-Miravet; Julian Guarque-Chabrera Journal: Neuroinformatics Date: 2019-07
Authors: Megan L Slaker; Emily T Jorgensen; Deborah M Hegarty; Xinyue Liu; Yan Kong; Fuming Zhang; Robert J Linhardt; Travis E Brown; Sue A Aicher; Barbara A Sorg Journal: eNeuro Date: 2018-10-04