Departament de Psicobiologia i Metodologia en Ciències de Salut, Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
Behav Brain Res. 2011 Jan 20;216(2):705-11. doi: 10.1016/j.bbr.2010.09.018. Epub 2010 Oct 8.
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.
最近的研究结果表明，神经甾体作为 GABAA 调节剂，如别孕烯醇酮（AlloP），不仅在大脑发育中发挥重要作用，特别是在海马体的成熟过程中，而且在成年行为中也发挥作用。本研究旨在探讨成年海马 CA1 内给予别孕烯醇酮和孕烯醇酮硫酸盐（PregS），分别为 GABAA 阳性和阴性调节剂，对在旷场试验中测量的行为新颖性反应的影响是否可能因新生儿时期（增加或减少）生理别孕烯醇酮水平的变化而不同。新生大鼠从第五天到第九天接受别孕烯醇酮和 5α-还原酶抑制剂（非那雄胺）。成熟时，双侧套管植入海马（CA1）。在新生对照组大鼠中，海马内给予别孕烯醇酮和 PregS 可降低总运动活性。相反，在新生别孕烯醇酮大鼠中，只有 PregS 降低了旷场活动，而在新生非那雄胺大鼠中，海马内注射（别孕烯醇酮和 PregS）不影响运动活性。此外，在新生别孕烯醇酮大鼠中，PregS 输注引起的活性降低高于对照组。然而，新生儿处理并未影响任何焦虑评分。尽管海马内给予别孕烯醇酮和 PregS 可降低内活动和前 5 分钟的时间，但极低的内值不允许得出焦虑作用的结论。结果表明，新生别孕烯醇酮给药增强了成年海马内给予 PregS 对旷场运动的作用，而新生非那雄胺给药则降低了这种作用，表明存在神经生物学适应，直至成年。
