title: Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats.
abstract: Perinatal asphyxia (PA) increases the likelihood of suffering from dopamine-related disorders, such as ADHD and schizophrenia. Since dopaminergic transmission plays a major role in cocaine sensitization, the purpose of this study was to determine whether PA could be associated with altered behavioral sensitization to cocaine. To this end, adult rats born vaginally (CTL), by caesarean section (C+), or by C+ with 15 min (PA15, moderate PA) or 19 min (PA19, severe PA) of global anoxia were repeatedly administered with cocaine (i.p., 15 mg/kg) and then challenged with cocaine (i.p., 15 mg/kg) after a 5-day withdrawal period. In addition, c-Fos, FosB/ΔFosB, DAT, and TH expression were assessed in dorsal (CPu) and ventral (NAcc) striatum. Results indicated that PA15 rats exhibited an increased locomotor sensitization to cocaine, while PA19 rats displayed an abnormal acquisition of locomotor sensitization and did not express a sensitized response to cocaine. c-Fos expression in NAcc, but not in CPu, was associated with these alterations in cocaine sensitization. FosB/ΔFosB expression was increased in all groups and regions after repeated cocaine administration, although it reached lower expression levels in PA19 rats. In CTL, C+, and PA15, but not in PA19 rats, the expression of TH in NAcc was reduced in groups repeatedly treated with cocaine, independently of the challenge test. Furthermore, this reduction was more pronounced in PA15 rats. DAT expression remained unaltered in all groups and regions studied. These results suggest that moderate PA may increase the vulnerability to drug abuse and in particular to cocaine addiction.
authors: Instituto de Investigaciones "Prof. Dr. Alberto C. Taquini"-ININCA, Facultad de Medicina, UBA-CONICET, Marcelo T. de Alvear 2270, C1122AAJ, Ciudad de Buenos Aires, Argentina.
authors: Pablo
authors: P
authors: Galeano
authors: Juan Ignacio
authors: JI
authors: Romero
authors: María Jesús
authors: MJ
authors: Luque-Rojas
authors: Juan
authors: J
authors: Suárez
authors: Mariana Inés
authors: MI
authors: Holubiec
authors: Verónica
authors: V
authors: Bisagno
authors: Luis Javier
authors: LJ
authors: Santín
authors: Fernando Rodríguez
authors: FR
authors: De Fonseca
authors: Francisco
authors: F
authors: Capani
authors: Eduardo
authors: E
authors: Blanco
mesh_terms: D000818:Animals; D001238:Asphyxia Neonatorum / Q000150:complications*; D059333:Central Nervous System Sensitization; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008124:Locomotion; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C483820:Fosb protein, rat; D016760:Proto-Oncogene Proteins c-fos; D014446:Tyrosine 3-Monooxygenase; D003042:Cocaine
keywords: c-Fos; caudate-putamen; cocaine sensitization; deltaFosB; dopamine transporter; nucleus accumbens; perinatal asphyxia; tyrosine hydroxylase