Interaction between early postnatal neurosteroid manipulations and adult infusion of neurosteroids into CA1 hippocampal region on the open field behaviour

Recent findings suggest that neurosteroids acting as GABAA modulators, as allopregnanolone (AlloP), not only play an important role in brain development, especially in the maturation of the hippocampus, but also in adult behaviour. The aim of the present work is to investigate whether the effects of adult CA1 intrahippocampal administrations of AlloP and pregnenolone sulphate (PregS), GABAA positive and negative modulators, respectively, on behavioural novelty responses measured in the open field test can be different depending on neonatal alterations (increase or decrease) of physiological AlloP levels. Rat pups received AlloP and a 5alpha-reductase inhibitor (finasteride) from the fifth to the ninth postnatal day. At maturity, a bilateral cannula was implanted into the hippocampus (CA1). Intrahippocampal AlloP and PregS decreased total locomotor activity in neonatal control rats. Instead, in neonatal AlloP rats only PregS decreased open field activity, whereas in neonatal finasteride rats the intrahippocampal injections (AlloP and PregS) did not affect locomotor activity. Also, the decrease in activity induced by PregS infusion was higher in neonatal AlloP rats than in controls. However, neonatal treatments did not affect any of the anxiety scores. Although intrahippocampal AlloP and PregS decreased inner activity and time spent in the first 5 min independently of the neonatal treatment, the extremely low inner values do not allow a conclusion of anxiogenic effects. Results indicate that neonatal AlloP administration potentiates and neonatal finasteride decreases the effects of adult intrahippocampal PregS administration on open field locomotion, suggesting neurobiological adaptations that remain until adult age. (C) 2010 Elsevier B.V. All rights reserved.