Mild and severe perinatal asphyxia induce opposite effects on cocaine sensitization in adult rats

GALEANO, PABLO; BLANCO CALVO, EDUARDO; BISAGNO, VERÓNICA; ROMERO, JUAN IGNACIO; HOLUBIEC, MARIANA INÉS; SARACENO, GUSTAVO EZEQUIEL; LUQUE ROJAS, MARÍA JESÚS; RODRÍGUEZ DE FONSECA, FERNANDO; CAPANI, FRANCISCO

Cancún

Congreso; First Meeting of the Federation of Neuroscience Societies in Latin America, the Caribbean and the Iberian Peninsula (FALAN); 2012

Federation of Neuroscience Societies in Latin America, the Caribbean and the Iberian Peninsula (FALAN)

Perinatal asphyxia (PA) is an obstetric complication that has been associated with an increased risk to develop dopamine-related disorders, such as attention deficit hyperactivity disorder (ADHD) and schizophrenia. Dysregulation of dopaminergic transmission is one of the long-lasting consequences of PA in the central nervous system. Since the dopaminergic system plays a major role in addiction processes, we hypothesized that PA could be associated with an increased vulnerability to psychostimulant addiction, particularly cocaine addiction. In the present work, we studied the behavioral sensitization to cocaine in adult rats that had undergone 15 min (mild) or 19 min (severe) of birth asphyxia. In addition, changes in the expression of tyrosine hydroxylase (TH) in the striatum were measured. Experimental subjects consisted of rats born vaginally (CTL), by caesarean section (C+), or by caesarean section followed by 15 min (PA15) or 19 min (PA19) of asphyxia. At three months of age, cocaine-induced behavioral sensitization was evaluated and TH levels in striatum were determined by Western Blot analysis. During five consecutive days, all groups increased their locomotor activity in response to daily cocaine injections (15 mg/kg) (conditioning phase). Five days later, CTL and C+ rats displayed a robust locomotor sensitization to an acute priming dose of cocaine (15 mg/kg). However, the acute priming injection of cocaine elicited an attenuated sensitized response in PA19 rats, while PA15 rats displayed an exacerbated sensitized response. Expression of TH in the striatum was significantly lower in PA15 rats compared to all other groups. These results demonstrate that birth asphyxia induces opposite effects on behavioral sensitization to cocaine depending on its severity. In addition, this data suggest that the decreased TH levels in the striatum of PA15 rats could be associated with the displayed hypersensitized response. Supported by CONICET, University of Buenos Aires and grant PCI-A/023328/09.