title: Unaltered cocaine self-administration in the prenatal LPS rat model of schizophrenia.
abstract: Although cocaine abuse is up to three times more frequent among schizophrenic patients, it remains unclear why this should be the case and whether sex influences this relationship. Using a maternal immune activation model of schizophrenia, we tested whether animals at higher risk of developing a schizophrenia-like state are more prone to acquire cocaine self-administration behavior, and whether they show enhanced sensitivity to the reinforcing actions of cocaine or if they are resistant to extinction. Pregnant rats were injected with lipopolysaccharide on gestational day 15 and 16, and the offspring (both male and female) were tested in working memory (T-maze), social interaction and sensorimotor gating (prepulse inhibition of the acoustic startle response) paradigms. After performing these tests, the rats were subjected to cocaine self-administration regimes (0.5mg/kg), assessing their dose-response and extinction. Male rats born to dams administered lipopolysaccharide showed impaired working memory but no alterations to their social interactions, and both male and female rats showed prepulse inhibition deficits. Moreover, similar patterns of cocaine self-administration acquisition, responsiveness to dose shifts and extinction curves were observed in both control and experimental rats. These results suggest that the higher prevalence of cocaine abuse among schizophrenic individuals is not due to a biological vulnerability directly associated to the disease and that other factors (social, educational, economic, familial, etc.) should be considered given the multifactorial nature of this illness.
authors.affiliation: Department of Psychobiology, School of Psychology, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Santos-Toscano
authors.affiliation: Department of Psychobiology, School of Psychology, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain.
authors.forename: Érika
authors.initials: É
authors.lastname: Borcel
authors.affiliation: Department of Psychobiology, School of Psychology, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Ucha
authors.affiliation: Department of Psychobiology, School of Psychology, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Orihuel
authors.affiliation: Department of Psychobiology, School of Psychology, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Capellán
authors.affiliation: Department of Psychobiology, School of Psychology, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Roura-Martínez
authors.affiliation: Department of Psychobiology, School of Psychology, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain. Electronic address: eambrosio@psi.uned.es.
authors.forename: Emilio
authors.initials: E
authors.lastname: Ambrosio
authors.affiliation: Department of Psychobiology, School of Psychology, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain. Electronic address: ahiguera@psi.uned.es.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Higuera-Matas
mesh_terms: D000818:Animals; D001307:Auditory Perception; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000150:complications* / Q000523:psychology; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D005260:Female; D008070:Lipopolysaccharides; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000150:complications; D008570:Memory, Short-Term; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D065808:Prepulse Inhibition; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle; D012559:Schizophrenia / Q000150:complications*; D012565:Schizophrenic Psychology; D012646:Self Administration; D012727:Sex Characteristics
chemical_list: D018765:Dopamine Uptake Inhibitors; D008070:Lipopolysaccharides; D003042:Cocaine
keywords: Cocaine self-administration; Dual diagnosis; LPS; Schizophrenia; Sex differences; Working memory