Gordon J H, Perry K O
Brain Res Bull. 1983 Apr;10(4):425-8. doi: 10.1016/0361-9230(83)90137-5.
The administration of pharmacologic doses of estrogen results in a biphasic response in striatal dopamine sensitivity, as measured by apomorphine-induced stereotypy. At 24 hr after the last dose of estradiol benzoate (EB) there is a suppression of apomorphine-induced stereotypy, which is followed by an increased sensitivity to apomorphine at 48 hr. The dopamine hyposensitivity is reflected postsynaptically by an increased KD (i.e., decreased affinity) for 3H-spiroperidol binding to striatal membranes, while the hypersensitive phase is reflected by an increased Bmax for 3H-spiroperidol binding to striatal membranes. Presynaptically during the hyposensitive phase the tyrosine hydroxylase displayed a decreased KM for the pterine cofactor. The decreased KM for the cofactor was retained in the hypersensitive animals, however the Vmax for tyrosine hydroxylase was decreased during the hypersensitive phase of the EB-induced changes in dopamine sensitivity. The presynaptic or autoreceptor sensitivity of the dopamine neurons projecting to the striatum was assessed by determining the apomorphine IC50 value for the inhibition of synaptosomal tyrosine hydroxylase activity. Utilizing this assay the animals that were hyposensitive to dopamine showed a normal presynaptic sensitivity, while those animals that had developed a hypersensitivity to dopamine following EB were also hypersensitive to dopamine presynaptically.
通过阿扑吗啡诱导的刻板行为来衡量，给予药理剂量的雌激素会导致纹状体多巴胺敏感性出现双相反应。在末次注射苯甲酸雌二醇（EB）后24小时，阿扑吗啡诱导的刻板行为受到抑制，随后在48小时对阿扑吗啡的敏感性增加。多巴胺低敏反应在突触后表现为与纹状体膜结合的3H-螺哌啶醇的解离常数（KD）增加（即亲和力降低），而高敏阶段则表现为与纹状体膜结合的3H-螺哌啶醇的最大结合容量（Bmax）增加。在低敏阶段，突触前酪氨酸羟化酶对蝶呤辅因子的米氏常数（KM）降低。在高敏动物中，辅因子的KM降低得以保留，然而在EB诱导的多巴胺敏感性变化的高敏阶段，酪氨酸羟化酶的最大反应速度（Vmax）降低。通过测定抑制突触体酪氨酸羟化酶活性的阿扑吗啡半数抑制浓度（IC50）值，评估投射到纹状体的多巴胺神经元的突触前或自身受体敏感性。利用该测定方法，对多巴胺低敏的动物表现出正常的突触前敏感性，而那些在注射EB后对多巴胺产生高敏反应的动物在突触前对多巴胺也呈高敏状态。
