Zhang M, Creese I
Center for Molecular and Behavioral Neuroscience, Rutgers, State University of New Jersey, Newark 07102.
Neurosci Lett. 1993 Oct 29;161(2):223-6. doi: 10.1016/0304-3940(93)90299-z.
Intraventricular infusion of an antisense oligodeoxynucleotide corresponding to the rat dopamine D2 receptor mRNA reduced rat striatal D2 receptors by 485, as measured by homogenate binding assays, while D1, muscarinic, and serotonin 5-HT2 receptors were unaffected. D2 receptor autoradiography indicated a homogeneous down-regulation of about 50% throughout the striatum and over 70% in the nucleus accumbens. A random oligodeoxynucleotide failed to affect either striatal D2 or D1 receptor density. The antisense treatment inhibited the D2 receptor agonist quinpirole-induced locomotor activation, without altering grooming behavior induced by SKF38393, a D1 receptor agonist. Antisense treatment also elicited catalepsy and reduced spontaneous locomotor activity.
通过匀浆结合试验测定，向大鼠脑室内注入与大鼠多巴胺D2受体mRNA对应的反义寡脱氧核苷酸后，大鼠纹状体D2受体减少了48%，而D1、毒蕈碱和5-羟色胺5-HT2受体未受影响。D2受体放射自显影显示，整个纹状体均有均匀约50%的下调，伏隔核中下调超过70%。随机寡脱氧核苷酸对纹状体D2或D1受体密度均无影响。反义治疗抑制了D2受体激动剂喹吡罗诱导的运动激活，而不改变D1受体激动剂SKF38393诱导的理毛行为。反义治疗还引发了僵住症并降低了自发运动活性。
