Adolescent self-administration of the synthetic cannabinoid receptor agonist JWH-018 induces neurobiological and behavioral alterations in adult male mice
| dc.rights.license | open | en_US |
| dc.contributor.author | MARGIANI, Giulia | |
| dc.contributor.author | CASTELLI, Maria Paola | |
| dc.contributor.author | PINTORI, Nicholas | |
| dc.contributor.author | FRAU, Roberto | |
| dc.contributor.author | ENNAS, Maria Grazia | |
| dc.contributor.author | ORRU, Roberto | |
| dc.contributor.author | SERRA, Valentina | |
| dc.contributor.author | FIORILLO, Edoardo | |
| dc.contributor.author | FADDA, Paola | |
| hal.structure.identifier | Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB] | |
| dc.contributor.author | MARSICANO, Giovanni | |
| dc.contributor.author | DE LUCA, Maria Antonietta | |
| dc.date.accessioned | 2022-11-07T13:50:45Z | |
| dc.date.available | 2022-11-07T13:50:45Z | |
| dc.date.issued | 2022-10 | |
| dc.identifier.issn | 0000-3158 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/170217 | |
| dc.description.abstractEn | Rationale: The use of synthetic cannabinoid receptor agonists (SCRAs) is growing among adolescents, posing major medical and psychiatric risks. JWH-018 represents the reference compound of SCRA-containing products. Objectives: This study was performed to evaluate the enduring consequences of adolescent voluntary consumption of JWH-018. Methods: The reinforcing properties of JWH-018 were characterized in male CD1 adolescent mice by intravenous self-administration (IVSA). Afterwards, behavioral, neurochemical, and molecular evaluations were performed at adulthood. Results: Adolescent mice acquired operant behavior (lever pressing, Fixed Ratio 1–3; 7.5 µg/kg/inf); this behavior was specifically directed at obtaining JWH-018 since it increased under Progressive Ratio schedule of reinforcement, and was absent in vehicle mice. JWH-018 IVSA was reduced by pretreatment of the CB1-antagonist/inverse agonist AM251. Adolescent exposure to JWH-018 by IVSA increased, at adulthood, both nestlet shredding and marble burying phenotypes, suggesting long-lasting repetitive/compulsive-like behavioral effects. JWH-018 did not affect risk proclivity in the wire-beam bridge task. In adult brains, there was an increase of ionized calcium binding adaptor molecule 1 (IBA-1) positive cells in the caudate-putamen (CPu) and nucleus accumbens (NAc), along with a decrease of glial fibrillary acidic protein (GFAP) immunoreactivity in the CPu. These glial alterations in adult brains were coupled with an increase of the chemokine RANTES and a decrease of the cytokines IL2 and IL13 in the cortex, and an increase of the chemokine MPC1 in the striatum. Conclusions: This study suggests for the first time that male mice self-administer the prototypical SCRA JWH-018 during adolescence. The adolescent voluntary consumption of JWH-018 leads to long-lasting behavioral and neurochemical aberrations along with glia-mediated inflammatory responses in adult brains. © 2022, The Author(s). | |
| dc.language.iso | EN | en_US |
| dc.rights | Attribution 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
| dc.subject.en | 3 (1 Naphthoyl) 1 Pentylindole | |
| dc.subject.en | 6 Iodo 3 (4 Methoxybenzoyl) 2 Methyl 1 (2 Morpholinoethyl)Indole | |
| dc.subject.en | Adaptor Protein | |
| dc.subject.en | Cannabinoid 1 Receptor | |
| dc.subject.en | Cyclooxygenase 2 | |
| dc.subject.en | Excitatory Amino Acid Transporter 2 | |
| dc.subject.en | Glial Fibrillary Acidic Protein | |
| dc.subject.en | Interleukin 2 | |
| dc.subject.en | Interleukin 3 | |
| dc.subject.en | Ionized Calcium Binding Adaptor Molecule 1 | |
| dc.subject.en | Monocyte Chemotactic Protein 1 | |
| dc.subject.en | Unclassified Drug | |
| dc.subject.en | Calcium | |
| dc.subject.en | Calcium Carbonate | |
| dc.subject.en | Cannabinoid Receptor Agonist | |
| dc.subject.en | Glial Fibrillary Acidic Protein | |
| dc.subject.en | Indole Derivative | |
| dc.subject.en | Interleukin 13 | |
| dc.subject.en | Interleukin 2 | |
| dc.subject.en | Naphthalene Derivative | |
| dc.subject.en | Rantes | |
| dc.subject.en | Adolescent | |
| dc.subject.en | Adult | |
| dc.subject.en | Animal Cell | |
| dc.subject.en | Animal Experiment | |
| dc.subject.en | Animal Model | |
| dc.subject.en | Animal Tissue | |
| dc.subject.en | Behavior Assessment | |
| dc.subject.en | Behavior Disorder | |
| dc.subject.en | Brain Cortex | |
| dc.subject.en | Cd-1 Mouse | |
| dc.subject.en | Compulsion | |
| dc.subject.en | Controlled Study | |
| dc.subject.en | Dorsal Striatum | |
| dc.subject.en | Drug Self Administration | |
| dc.subject.en | Glia Cell | |
| dc.subject.en | Immunohistochemistry | |
| dc.subject.en | Immunoreactivity | |
| dc.subject.en | Male | |
| dc.subject.en | Marble Burying Test | |
| dc.subject.en | Nervous System Inflammation | |
| dc.subject.en | Neurobiology | |
| dc.subject.en | Neurochemistry | |
| dc.subject.en | Nonhuman | |
| dc.subject.en | Nucleus Accumbens | |
| dc.subject.en | Operant Conditioning | |
| dc.subject.en | Protein Expression | |
| dc.subject.en | Receptor Blocking | |
| dc.subject.en | Reinforcement (Psychology) | |
| dc.subject.en | Animal | |
| dc.subject.en | Calcium Carbonate | |
| dc.subject.en | Cannabinoid Receptor Agonists | |
| dc.subject.en | Chemokine Ccl5 | |
| dc.subject.en | Glial Fibrillary Acidic Protein | |
| dc.subject.en | Indoles | |
| dc.subject.en | Naphthalenes | |
| dc.subject.en | Receptor | |
| dc.subject.en | Cannabinoid | |
| dc.subject.en | 4 dichlorophenyl) 5 (4 iodophenyl) 4 methyl n (1 piperidyl) 1h pyrazole 3 carboxamide | |
| dc.title.en | Adolescent self-administration of the synthetic cannabinoid receptor agonist JWH-018 induces neurobiological and behavioral alterations in adult male mice | |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1007/s00213-022-06191-9 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC] | en_US |
| dc.identifier.pubmed | 35943523 | en_US |
| bordeaux.journal | Psychopharmacology | en_US |
| bordeaux.page | 3083-3102 | en_US |
| bordeaux.volume | 239 | en_US |
| bordeaux.hal.laboratories | Neurocentre Magendie - U1215 | en_US |
| bordeaux.issue | 10 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | INSERM | en_US |
| bordeaux.team | Endocannabinoïdes et Neuroadaptation | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.identifier.funderID | Università degli Studi di Cagliari | en_US |
| hal.identifier | hal-03842334 | |
| hal.version | 1 | |
| hal.date.transferred | 2022-11-07T13:51:00Z | |
| hal.export | true | |
| dc.rights.cc | CC BY | en_US |
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