title: Morphine-induced locomotor sensitization produces structural plasticity in the mesocorticolimbic system dependent on CB1-R activity.
abstract: Changes in structural plasticity produced by the chronic exposure to drugs of abuse, such as alterations in dendritic spine densities, participate in the development of maladaptive learning processes leading to drug addiction. Understanding the neurobiological mechanisms involved in these aberrant changes is crucial to clarify the neurobiological substrate of addiction. Drug-induced locomotor sensitization has been widely accepted as a useful animal model to study these mechanisms related to drug addiction. We have evaluated the changes in structural plasticity in the mesocorticolimbic system involved in morphine-induced locomotor sensitization. The role of the cannabinoid receptor type 1 (CB1-R) in these neuroplastic alterations has also been studied using CB1-R-deficient (CB1-R KO) mice. Structural plasticity changes promoted by morphine are a highly dynamic phenomenon that evolves during the entire time course of the behavioral sensitization in wild-type (WT) animals. The different phases of the sensitization process were related to specific changes in connectivity between neurons revealed by modifications in dendritic spines in specific areas of the mesocorticolimbic system. Moreover, the lack of morphine-induced locomotor sensitization in CB1-R KO mice was accompanied by abnormal alterations in structural plasticity in the same mesocorticolimbic areas. These specific structural plasticity changes mediated by CB1-R activity seem necessary for the normal progression of morphine-induced locomotor sensitization and could play a critical role in the addictive process.
authors.affiliation: Laboratory of Neuropharmacology, Parc de Recerca Biomèdica de Barcelona/Universitat Pompeu Fabra, Spain.
authors.forename: Thomas
authors.initials: T
authors.lastname: Guegan
authors.affiliation: Laboratory of Neuropharmacology, Parc de Recerca Biomèdica de Barcelona/Universitat Pompeu Fabra, Spain.
authors.forename: Joan Pau
authors.initials: JP
authors.lastname: Cebrià
authors.affiliation: Laboratory of Neuropharmacology, Parc de Recerca Biomèdica de Barcelona/Universitat Pompeu Fabra, Spain. rafael.maldonado@upf.edu.
authors.forename: Rafael
authors.initials: R
authors.lastname: Maldonado
authors.affiliation: Laboratory of Neuropharmacology, Parc de Recerca Biomèdica de Barcelona/Universitat Pompeu Fabra, Spain. miquel.martin@igf.cnrs.fr.
authors.forename: Miquel
authors.initials: M
authors.lastname: Martin
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D003712:Dendrites / Q000187:drug effects; D017353:Gene Deletion; D055785:Gene Knockdown Techniques; D008032:Limbic System / Q000033:anatomy & histology / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency / Q000235:genetics
chemical_list: D000701:Analgesics, Opioid; C543264:Cnr1 protein, rat; D043884:Receptor, Cannabinoid, CB1; D009020:Morphine
keywords: Addiction; cannabinoid type 1 receptor; dendritic spines; locomotor sensitization; opioid; structural plasticity