Llidó Anna, Bartolomé Iris, Darbra Sònia, Pallarès Marc
Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
Behav Brain Res. 2016 Aug 1;309:44-50. doi: 10.1016/j.bbr.2016.04.047. Epub 2016 Apr 29.
Endogenous levels of the neurosteroid (NS) allopregnanolone (AlloP) during neonatal stages are crucial for the correct development of the central nervous system (CNS). In a recent work we reported that the neonatal administration of AlloP or finasteride (Finas), an inhibitor of the enzyme 5α-reductase needed for AlloP synthesis, altered the voluntary consumption of ethanol and the ventrostriatal dopamine (DA) levels in adulthood, suggesting that neonatal NS manipulations can increase alcohol abuse vulnerability in adulthood. Moreover, other authors have associated neonatal NS alterations with diverse dopaminergic (DAergic) alterations. Thus, the aim of the present work is to analyse if manipulations of neonatal AlloP alter the DAergic response in the nucleus accumbens (NAcc) during alcohol intake in rats. We administered AlloP or Finas from postnatal day (PND) 5 to PND9. At PND98, we measured alcohol consumption using a two-bottle free-choice model (ethanol 10% (v/v)+glucose 3% (w/v), and glucose 3% (w/v)) for 12 days. On the last day of consumption, we measured the DA and 3,4-dihydroxyphenylacetic acid (DOPAC) release in NAcc in response to ethanol intake. The samples were obtained by means of in vivo microdialysis in freely moving rats, and DA and DOPAC levels were determined by means of high-performance liquid chromatography analysis (HPLC). The results revealed that neonatal Finas increased ethanol consumption in some days of the consumption phase, and decreased the DA release in the NAcc in response to solutions (ethanol+glucose) and food presentation. Taken together, these results suggest that neonatal NS alterations can affect alcohol rewarding properties.
新生儿期神经甾体（NS）别孕烯醇酮（AlloP）的内源性水平对于中枢神经系统（CNS）的正常发育至关重要。在最近的一项研究中，我们报告称，新生儿期给予AlloP或非那雄胺（Finas，AlloP合成所需的5α-还原酶抑制剂）会改变成年期乙醇的自愿摄入量以及腹侧纹状体多巴胺（DA）水平，这表明新生儿期NS的操控会增加成年期酒精滥用的易感性。此外，其他作者已将新生儿期NS改变与多种多巴胺能（DAergic）改变联系起来。因此，本研究的目的是分析新生儿期AlloP的操控是否会改变大鼠在酒精摄入期间伏隔核（NAcc）中的DAergic反应。我们从出生后第5天（PND）至第9天给予AlloP或Finas。在PND98时，我们使用双瓶自由选择模型（10%（v/v）乙醇+3%（w/v）葡萄糖，以及3%（w/v）葡萄糖）测量酒精摄入量，持续12天。在摄入的最后一天，我们测量了NAcc中响应乙醇摄入的DA和3,4-二羟基苯乙酸（DOPAC）释放。通过对自由活动大鼠进行体内微透析获得样本，并通过高效液相色谱分析（HPLC）测定DA和DOPAC水平。结果显示，新生儿期Finas在摄入阶段的某些日子增加了乙醇摄入量，并降低了NAcc中响应溶液（乙醇+葡萄糖）和食物呈现的DA释放。综上所述，这些结果表明新生儿期NS改变会影响酒精的奖赏特性。
