title: Role of dopamine neurotransmission in the long-term effects of repeated social defeat on the conditioned rewarding effects of cocaine.
abstract: Numerous studies report that social defeat stress alters dopamine (DA) neurotransmission in several areas of the brain. Alterations of the mesolimbic dopaminergic pathway are believed to be responsible for the increased vulnerability to drug use observed as a result of social stress. In the present study, we evaluated the influence of DA receptors on the long-term effect of repeated social defeat (RSD) on the conditioned rewarding and reinstating effects of cocaine. For this purpose, the D1R antagonist SCH 23390 and the D1R antagonist raclopride were administered 30min before each social defeat and a cocaine-induced CPP procedure was initiated three weeks later. The expression of the D1R and D2R was also measured in the cortex and hippocampus throughout the entire procedure. Mice exposed to RSD showed an increase in the conditioned rewarding effects of cocaine that was blocked by both DA receptors antagonists when a subthreshold dose of cocaine was employed. However, while the vulnerability to reinstatement of the preference induced by 25mg/kg cocaine-induced CPP was abolished by the D1R antagonist, it was practically unaffected by raclopride. Increases in D2R receptor levels were observed in the cortex of defeated animals after the first and fourth social defeats and in the hippocampus 3weeks later. Nevertheless, D1R receptor levels in the hippocampus decreased only after the last social defeat. Our results confirm that RSD enhances the conditioned rewarding effects of cocaine and that both DA receptors are involved in this enduring effect of social stress.
authors.affiliation: Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez 21, 46010 Valencia, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Montagud-Romero
authors.affiliation: Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez 21, 46010 Valencia, Spain.
authors.forename: M D
authors.initials: MD
authors.lastname: Reguilon
authors.affiliation: Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez 21, 46010 Valencia, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Roger-Sanchez
authors.affiliation: Department of Molecular and Cellular Pathology of Alcohol, Príncipe Felipe Research Center, C/Eduardo Primo Yúfera 3, 46012 Valencia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Pascual
authors.affiliation: Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez 21, 46010 Valencia, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Aguilar
authors.affiliation: Department of Molecular and Cellular Pathology of Alcohol, Príncipe Felipe Research Center, C/Eduardo Primo Yúfera 3, 46012 Valencia, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Guerri
authors.affiliation: Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez 21, 46010 Valencia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Miñarro
authors.affiliation: Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez 21, 46010 Valencia, Spain. Electronic address: marta.rodriguez@uv.es.
authors.forename: M
authors.initials: M
authors.lastname: Rodríguez-Arias
mesh_terms: D000367:Age Factors; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects*; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D020891:Raclopride / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000235:genetics / Q000378:metabolism; D012201:Reward; D018709:Statistics, Nonparametric; D013315:Stress, Psychological / Q000473:pathology*
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D011954:Receptors, Dopamine; C534628:SCH 23390; D020891:Raclopride; D003042:Cocaine
keywords: Cocaine; Conditioned place preference; Dopamine receptors; Social defeat stress