title: Maternal Separation Impairs Cocaine-Induced Behavioural Sensitization in Adolescent Mice.
abstract: Adverse early-life conditions induce persistent disturbances that give rise to negative emotional states. Therefore, early life stress confers increased vulnerability to substance use disorders, mainly during adolescence as the brain is still developing. In this study, we investigated the consequences of maternal separation, a model of maternal neglect, on the psychotropic effects of cocaine and the neuroplasticity of the dopaminergic system. Our results show that mice exposed to maternal separation displayed attenuated behavioural sensitization, while no changes were found in the rewarding effects of cocaine in the conditioned place preference paradigm and in the reinforcing effects of cocaine in the self-administration paradigm. The evaluation of neuroplasticity in the striatal dopaminergic pathways revealed that mice exposed to maternal separation exhibited decreased protein expression levels of D2 receptors and increased levels of the transcriptional factor Nurr1. Furthermore, animals exposed to maternal separation and treated with cocaine exhibited increased DA turnover and protein expression levels of DAT and D2R, while decreased Nurr1 and Pitx3 protein expression levels were observed when compared with saline-treated mice. Taken together, our data demonstrate that maternal separation caused an impairment of cocaine-induced behavioural sensitization possibly due to a dysfunction of the dopaminergic system, a dysfunction that has been proposed as a factor of vulnerability for developing substance use disorders.
authors.affiliation: Neurobiology of Behavior Research Group (GReNeC). Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Gracia-Rubio
authors.affiliation: Group of Cellular and Molecular Pharmacology, Faculty of Medicine, University of Murcia, Murcia, Spain.|Instituto Murciano de Investigación Biosanitaria (IMIB), Murcia, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Martinez-Laorden
authors.affiliation: Neurobiology of Behavior Research Group (GReNeC). Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Moscoso-Castro
authors.affiliation: Group of Cellular and Molecular Pharmacology, Faculty of Medicine, University of Murcia, Murcia, Spain.|Instituto Murciano de Investigación Biosanitaria (IMIB), Murcia, Spain.
authors.forename: M Victoria
authors.initials: MV
authors.lastname: Milanés
authors.affiliation: Group of Cellular and Molecular Pharmacology, Faculty of Medicine, University of Murcia, Murcia, Spain.|Instituto Murciano de Investigación Biosanitaria (IMIB), Murcia, Spain.
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Laorden
authors.affiliation: Neurobiology of Behavior Research Group (GReNeC). Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.|Neuroscience Research Program. IMIM (Hospital del Mar Research Institute) Barcelona, Spain.
authors.forename: Olga
authors.identifier: 0000-0003-2264-7852
authors.initials: O
authors.lastname: Valverde
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism; D008297:Male; D008426:Maternal Deprivation; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009434:Neural Pathways / Q000187:drug effects; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012201:Reward; D012646:Self Administration; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D018398:Homeodomain Proteins; C539883:Nr4a2 protein, mouse; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D017448:Receptors, Dopamine D2; D014157:Transcription Factors; C433629:homeobox protein PITX3; D003042:Cocaine