Dilts R P, Novitzki M R, Phan T H, Corley K C, Boadle-Biber M C
Department of Physiology, School of Medicine, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0551, USA.
Brain Res. 1996 Dec 2;742(1-2):294-8. doi: 10.1016/s0006-8993(96)01018-9.
Previous studies indicate that exposure of rats to randomly presented, inescapable loud sound, referred to as sound stress, increases central serotonin turnover as well as the ex vivo activity of tryptophan hydroxylase (EC 1.14.16.4), the rate-limiting enzyme in serotonin biosynthesis. The purpose of this investigation was to determine whether intracerebroventricular (i.c.v.) administration of neurotensin (NT), a tridecapeptide found within the midbrain raphe, influences the activation of the midbrain serotonergic neurons by sound stress. Accumulation of 5-hydroxytryptophan (5-HTP) in vivo, in the presence of the aromatic amino acid decarboxylase inhibitor, NSD 1015 (m-hydroxybenzylhydrazine, 100 mg/kg i.p.) given immediately before a 30 min sound stress, was used as an index of in vivo tryptophan hydroxylase activity. Sound-stressed rats had significantly higher levels of 5-HTP in cortex and midbrain compared to sham-stressed controls. NT (0.01-3.3 nmol total), given i.c.v., 5 min prior to 30 min sound stress, completely blocked the enhanced accumulation of 5-HTP, but had no effect on basal accumulation of 5-HTP, except at the highest doses of 1.0 or 3.3 nmol, which others have previously shown to inhibit basal serotonergic metabolism. NT (0.3 and 3.3 nmol) blocked the increase in cortical tryptophan hydroxylase activity, ex vivo, in response to 30 min sound stress, without affecting basal enzyme activity. These and other recent data suggest a possible role for endogenous NT in the regulation of serotonergic neuronal activity within the midbrain raphe.
先前的研究表明，将大鼠暴露于随机出现的、无法逃避的响亮声音（即声音应激）中，会增加中枢5-羟色胺周转率以及色氨酸羟化酶（EC 1.14.16.4）的体外活性，色氨酸羟化酶是5-羟色胺生物合成中的限速酶。本研究的目的是确定脑室内（i.c.v.）注射神经降压素（NT）（一种存在于中脑缝际核的十三肽）是否会影响声音应激对中脑5-羟色胺能神经元的激活作用。在30分钟声音应激前立即腹腔注射芳香族氨基酸脱羧酶抑制剂NSD 1015（间羟基苄基肼，100mg/kg），体内5-羟色氨酸（5-HTP）的积累被用作体内色氨酸羟化酶活性的指标。与假应激对照组相比，声音应激大鼠的皮质和中脑中5-HTP水平显著更高。在30分钟声音应激前5分钟经脑室内注射NT（总量0.01 - 3.3nmol），可完全阻断5-HTP积累的增强，但对5-HTP的基础积累无影响，不过在最高剂量1.0或3.3nmol时除外，此前其他研究表明该剂量会抑制基础5-羟色胺能代谢。NT（0.3和3.3nmol）可阻断体外皮质色氨酸羟化酶活性因30分钟声音应激而增加，且不影响基础酶活性。这些以及其他近期数据表明内源性NT在调节中脑缝际核内5-羟色胺能神经元活性方面可能发挥作用。
