NEUROCHEMICAL AND BEHAVIORAL-EFFECTS OF ACUTE AND CHRONIC TREATMENT WITH APOMORPHINE IN RATS
NEUROCHEMICAL AND BEHAVIORAL-EFFECTS OF ACUTE AND CHRONIC TREATMENT WITH APOMORPHINE IN RATS
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DOI：
10.1016/0028-3908(91)90203-n
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发表时间：
1991-02-01
影响因子：
4.7
通讯作者：
BARDO, MT
中科院分区：
文献类型：
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作者：
ROWLETT, JK;MATTINGLY, BA;BARDO, MT
在三个实验中，每天一次给大鼠注射5.0 mg/kg阿扑吗啡或赋形剂，并测试10-14天的自发活动。 在每个实验中，阿扑吗啡产生行为敏化，其特征在于随着每次后续注射，自发活动逐渐增加。 在测试的第11天，在设计用于评估多巴胺（DA）合成的实验中，向大鼠注射5.0 mg/kg阿扑吗啡或载体，随后注射100 mg/kg NSD-1015（一种酶L-芳香族氨基酸脱羧酶的抑制剂）。 给药NSD-1015后，通过高效液相色谱法（HPLC）和电化学检测法测定纹状体和中脑边缘组织中二羟基苯丙氨酸（DOPA）的浓度。 结果表明，阿扑吗啡急性治疗后，纹状体和中脑边缘组织中多巴的积累显着减少。 更重要的是，阿扑吗啡慢性治疗产生了显着增加多巴在这两个领域的积累。 在随后的实验中，在试验的第14天处死大鼠，以测定纹状体和中脑边缘区中DA、3，4-二羟基苯乙酸（DOPAC）或[H-3]螺哌隆的特异性结合水平。 虽然DOPAC的水平显着降低后，急性注射阿扑吗啡的大脑区域，阿扑吗啡的慢性治疗没有显着影响DA，DOPAC或[H-3]螺哌隆的特异性结合的水平。 这些发现表明，阿扑吗啡的行为敏感化的发展可能与DA合成的改变有关。
In three experiments, rats were injected once daily with 5.0 mg/kg apomorphine or vehicle and tested for locomotor activity for 10-14 days. In each experiment, apomorphine produced behavioral sensitization, characterized by a progressively greater increase in locomotor activity with each succeeding injection. On day 11 of testing, in an experiment designed to assess the synthesis of dopamine (DA), rats were injected with 5.0 mg/kg apomorphine or vehicle, followed by 100 mg/kg NSD-1015, an inhibitor of the enzyme l-aromatic amino acid decarboxylase. After administration of NSD-1015, concentrations of dihydroxyphenylalanine (DOPA) were determined in striatal and mesolimbic tissues by high performance liquid chromatography (HPLC) with electrochemical detection. The results revealed a significant decrease in accumulation of DOPA in both striatal and mesolimbic tissue after acute treatment with apomorphine. More important, chronic treatment with apomorphine produced a significant increase in accumulation of DOPA in both areas. In subsequent experiments, rats on day 14 of testing were sacrificed for determination of levels of DA, 3,4-dihydroxyphenylacetic acid (DOPAC) or specific binding of [H-3]spiperone in the striatum and mesolimbic region. Although levels of DOPAC were significantly reduced in the regions of the brain after an acute injection of apomorphine, chronic treatment with apomorphine did not significantly affect levels of DA, DOPAC or specific binding of [H-3]spiperone. These findings suggest that the development of behavioral sensitization to apomorphine may be related to an alteration in the synthesis of DA.