title: Long-term effects of repeated social stress on the conditioned place preference induced by MDMA in mice.
abstract: Previous studies have demonstrated that social defeat stress increases the rewarding effects of psychostimulant drugs such as cocaine and amphetamine. In the present study we evaluated the long-term effects of repeated social defeat (RSD) on the rewarding effects of ±3,4-methylenedioxymethamphetamine (MDMA) hydrochloride in the conditioned place preference (CPP) paradigm. Adolescent and young adult mice were exposed to four episodes of social defeat (on PND 29-40 and PND 47-56, respectively) and were conditioned three weeks later with 1.25 or 10mg/kg i.p. of MDMA (experiment 1). The long-term effects of RSD on anxiety, social behavior and cognitive processes were also evaluated in adult mice (experiment 2). RSD during adolescence enhanced vulnerability to priming-induced reinstatement in animals conditioned with 1.25mg/kg of MDMA and increased the duration of the CPP induced by the 10mg/kg of MDMA. The latter effect was also observed after RSD in young adult mice, as well as an increase in anxiety-like behavior, an alteration in social interaction (reduction in attack and increase in avoidance/flee and defensive/submissive behaviors) and an impairment of maze learning. These results support the idea that RSD stress increases the rewarding effects of MDMA and induces long-term alterations in anxiety, learning and social behavior in adult mice. Thus, exposure to stress may increase the vulnerability of individuals to developing MDMA dependence, which is a factor to be taken into account in relation to the prevention and treatment of this disorder.
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiologia, Facultad de Psicología, Universidad de Valencia, Spain.
authors.forename: M P
authors.initials: MP
authors.lastname: García-Pardo
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiologia, Facultad de Psicología, Universidad de Valencia, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Blanco-Gandía
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiologia, Facultad de Psicología, Universidad de Valencia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Valiente-Lluch
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiologia, Facultad de Psicología, Universidad de Valencia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Rodríguez-Arias
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiologia, Facultad de Psicología, Universidad de Valencia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Miñarro
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiologia, Facultad de Psicología, Universidad de Valencia, Spain. Electronic address: asuncion.aguilar@uv.es.
authors.forename: M A
authors.initials: MA
authors.lastname: Aguilar
mesh_terms: D000305:Adrenal Cortex Hormones / Q000097:blood; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects; D006213:Hallucinogens / Q000494:pharmacology*; D007398:Interpersonal Relations; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D012054:Reinforcement, Psychology; D013315:Stress, Psychological / Q000503:physiopathology* / Q000523:psychology
chemical_list: D000305:Adrenal Cortex Hormones; D006213:Hallucinogens; D018817:N-Methyl-3,4-methylenedioxyamphetamine
keywords: Adolescence; Conditioned place preference; MDMA; Mice; Repeated social defeat