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[P2.42]: Neonatal finasteride administration disrupts prepulse inhibition in adulthood
Author(s) -
Darbra S.,
Pallarès M.
Publication year - 2010
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2010.07.172
Subject(s) - prepulse inhibition , citation , library science , finasteride , psychology , medicine , computer science , psychiatry , prostate , schizophrenia (object oriented programming) , cancer
Neurosteroids that act as GABAA modulators, as allopregnanolone (AlloP), not only play important roles in brain development, and specially in the maturation of the hippocampus, but also in adult behaviour. The aim of the present work is to screen whether developmentally altered neurosteroid levels influence the normal behavioural response to novelty measured in the open field test after adult intrahippocampal administrations of AlloP, a GABAA positive modulating neurosteroid, or pregnenolone sulphate (PregS), a GABAA negative modulator. Pups received AlloP (10 mg/kg, s.c.), a 5alpha-reductase inhibitor (finasteride, 50 mg/kg, s.c.) or vehicle from the fifth to the ninth postnatal day. At 90 days old a bilateral cannula was implanted into the hippocampus. After recovery, animals received AlloP (0.2 g/0.5 l), PregS (5 ng/0.5 l) or vehicle in each hippocampus 5 min before they were tested. Intrahippocampal AlloP and PregS decreased total novelty-directed locomotor activity in neonatal control rats. Instead, in neonatal AlloP-treated rats only PregS decreased open field activity, whereas in neonatal finasteride treated rats the intrahippocampal injections had no effects. The decreased of activity induced by intrahippocampal PregS injection was higher in neonatal AlloP-treated rats than in controls. Neonatal treatments did not affect anxiety relevant scores (inner activity, time spent in and number of entries into the inner zone in the first five minutes). Intrahippocampal AlloP and PregS decreased, however, inner activity and time spent in the inner zone independently of the neonatal treatment. But since the overall activity is reduced, the reduced activity in the centre could be suggest more an overall reduction in motor activity (or exploratory drive) than increased anxiety. Results indicate that the effects of intrahippocampal neurosteroids administration on novelty-directed activity are different in function of the neonatal treatment, possibly related to alterations in hippocampal GABAA receptors maturation, suggesting neurobiological adaptations that remain until the adulthood.