Altered cocaine-induced behavioral sensitization in severe perinatal asphyxia.

P. GALEANO; E. BLANCO-CALVO; J. ROMERO; M. LUQUE-ROJAS; V. BISAGNO; G. N. BALERIO; L. SANTÍN; F. RODRÍGUEZ DE FONSECA; F. CAPANI

San Diego, USA

Congreso; 2010 SFN Annual Meeting; 2010

Society for Neuroscience

Abstract: Alterations of the mesocorticolimbic dopaminergic pathway have been described in the rat model of perinatal asphyxia developed by Bjelke (1991). Also, it has been shown that a mild perinatal asphyxia exacerbates amphetamine/methamphetamine-induced hyperlocomotion (Boksa and El-Khodor, 1998; Juárez et al., 2003; Wakuda et al., 2008) while a severe perinatal asphyxia blocks its expression (Chen et al., 1995).In the present work, we studied the cocaine-conditioned locomotion and cocaine-induced psychomotor sensitization in young adult rats that had undergone severe perinatal asphyxia. Asphyctic male rats (PA, n =34) were obtained by immersing foetuses-containing uterine horns, removed from Sprague-Dawley rats that had vaginally delivered immediately before no more than two pups, into a water bath at 37 ºC for 19 min (severe perinatal asphyxia). Control male subjects (CTL, n = 38) were born by vaginal delivery from other dams (see Capani et al., 2009). At two months of age, half of the animals in each group received an intraperitoneal injection of cocaine (Coc, 15 mg/kg) and the other half received saline injections (Vhi). Immediately after the injection of Coc or Vhi, rats were placed in an Open Field (60 x 60 cm) and locomotion was registered by a computerized videotracking system (SMART) for 30 min. This treatment was repeated once daily for five consecutive days (acquisition phase) followed by 5 days in which animals were left undisturbed (resting phase). At day 11 Conditioned Locomotion was assessed by re-exposing the animals to the Open Field (30 min) immediately after a single saline injection and the expression of Behavioral Sensitization was evoked 24 hs later, by a challenge dose of cocaine (7.5 mg/kg). During acquisition phase, both CTL and AP rats injected with Coc progressively increased the locomotor activity, there being no significant differences between them. Also, both groups increased significantly the locomotor activity, in comparison to Vhi groups, when they were re-exposed to Open Field after a single saline injection (Conditioned Locomotion). However a challenge injection of cocaine (day 12) elicited a strong behavioral sensitization effect in CTL but not in PA rats. These results extended those of Chen et al. (1995) who reported a lack of an exaggerated behavioral response to an acute administration of amphetamine in severe perinatal asphyxia, in comparison to mild asphyxia. Here, it is shown that Behavioural Sensitization is also impaired, demostrating that severe perinatal asphyxia seems to produce long-lasting specific deleterious effects in the reward system, probably due to alterations of the mesocorticolimbic dopaminergic system.