Serra M, Sanna E, Mostallino M C, Biggio G
Department of Experimental Biology, Center of Excellence for Neurobiology of Dependence, University of Cagliari, Cagliari 09100, Italy.
Eur Neuropsychopharmacol. 2007 Jan;17(1):1-11. doi: 10.1016/j.euroneuro.2006.03.004. Epub 2006 Apr 19.
Social isolation of rats immediately after weaning is associated to a reduction in the cerebrocortical and plasma concentrations of progesterone and its metabolites 3alpha,5alpha-TH PROG and 3alpha,5alpha-THDOC. Although we found that the basal plasma concentration of adrenocorticotropic hormone in isolated rats was slightly decreased compared with that in group-housed animals no other significant changes were found in the steroidogenic machinery (peripheral benzodiazepine receptors, steroidogenic regulatory protein (StAR)). However, the functional response of the hypothalamic-pituitary-adrenal axis HPA axis to an acute stressful stimulus (foot shock), or to an acute injection of ethanol or isoniazid is markedly increased in isolated rats. Behavioral studies have also indicated that the ability of ethanol to inhibit isoniazid-induced convulsions is greater in isolated rats than in group-housed animals and this effect of isolation is prevented by treatment with the 5alpha-reductase inhibitor finasteride. Social isolation modified the effects of ethanol on the amounts of StAR mRNA and protein in the brain suggesting an alteration in the mechanism of cholesterol transport in mitochondria. Moreover, the amounts of the alpha4 and delta subunits of the GABA(A) receptor in the hippocampus were increased in isolated rats, and these effects were accompanied by an increase in GABA(A) receptor-mediated tonic inhibitory currents in granule cells of the dentate gyrus. Ethanol also increased the amplitude of GABA(A) receptor-mediated miniature inhibitory postsynaptic currents (mIPSC) recorded from CA1 pyramidal neurons with a greater potency in hippocampal slices prepared from socially isolated rats than in those from group-housed, an effect inhibited by finasteride.
大鼠断奶后立即进行社会隔离，与脑皮质和血浆中孕酮及其代谢产物3α,5α-四氢孕酮（3α,5α-TH PROG）和3α,5α-四氢脱氧皮质酮（3α,5α-THDOC）浓度降低有关。尽管我们发现，与群居动物相比，隔离大鼠促肾上腺皮质激素的基础血浆浓度略有降低，但在类固醇生成机制（外周苯二氮䓬受体、类固醇生成调节蛋白（StAR））方面未发现其他显著变化。然而，在隔离大鼠中，下丘脑-垂体-肾上腺轴（HPA轴）对急性应激刺激（足部电击）、急性注射乙醇或异烟肼的功能反应明显增强。行为学研究还表明，乙醇抑制异烟肼诱发惊厥的能力在隔离大鼠中比在群居动物中更强，而5α-还原酶抑制剂非那雄胺治疗可预防这种隔离效应。社会隔离改变了乙醇对脑中StAR mRNA和蛋白含量的影响，提示线粒体中胆固醇转运机制发生改变。此外，隔离大鼠海马中GABA(A)受体的α4和δ亚基含量增加，这些效应伴随着齿状回颗粒细胞中GABA(A)受体介导的强直抑制电流增加。乙醇还增加了从CA1锥体神经元记录到的GABA(A)受体介导的微小抑制性突触后电流（mIPSC）的幅度，在社会隔离大鼠制备的海马切片中比在群居大鼠制备的切片中作用更强，非那雄胺可抑制这种效应。
