Ghelardini C, Galeotti N, Matucci R, Bellucci C, Gualtieri F, Capaccioli S, Quattrone A, Bartolini A
Department of Pharmacology, University of Florence, Italy.
Neuropharmacology. 1999 Mar;38(3):339-48. doi: 10.1016/s0028-3908(98)00194-4.
The effect on memory processes of inactivation of the M1 gene by an antisense oligodeoxyribonucleotide (aODN) was investigated in the mouse passive avoidance test. Mice received a single intracerebroventricular (i.c.v.) injection of M1 aODN (0.3, 1.0 or 2.0 nmol per injection), degenerated ODN (dODN) or vehicle on days 1, 4 and 7. An amnesic effect, comparable to that produced by antimuscarinic drugs, was observed 12, 24, 48 and 72 h after the last i.c.v. aODN injection, whereas dODN and vehicle, used as controls, did not produce any effect. Reduction in the entrance latency to the dark compartment induced by aODN disappeared 7 days after the end of aODN treatment, which indicates the absence of any irreversible damage or toxicity caused by aODN. Quantitative reverse transcription-polymerase chain reaction analysis demonstrated that a decrease in M1 mRNA levels occurred only in the aODN-treated group, being absent in all control groups. Furthermore, a reduction in M1 receptors was observed in the hippocampus of aODN-treated mice. Neither aODN, dODN nor vehicle produced any behavioral impairment of mice. These results indicate that the integrity and functionality of M1 receptors are fundamental in the modulation of memory processes.
在小鼠被动回避试验中，研究了反义寡脱氧核糖核苷酸（aODN）使M1基因失活对记忆过程的影响。在第1、4和7天，小鼠接受单次脑室内（i.c.v.）注射M1 aODN（每次注射0.3、1.0或2.0 nmol）、变性ODN（dODN）或溶剂。在最后一次i.c.v.注射aODN后12、24、48和72小时，观察到与抗毒蕈碱药物产生的失忆效应相当的效应，而作为对照的dODN和溶剂没有产生任何效应。aODN诱导的进入暗室潜伏期缩短在aODN治疗结束后7天消失，这表明aODN没有造成任何不可逆的损伤或毒性。定量逆转录-聚合酶链反应分析表明，仅在aODN处理组中出现M1 mRNA水平降低，所有对照组均未出现。此外，在aODN处理的小鼠海马中观察到M1受体减少。aODN、dODN和溶剂均未对小鼠造成任何行为损伤。这些结果表明，M1受体的完整性和功能对于记忆过程的调节至关重要。
