Wecker L, Mobley P L, Dettbarn W D
Arch Int Pharmacodyn Ther. 1977 May;227(1):69-75.
Rats were treated acutely (one day) and chronically (seven days) with atropine, paraoxon, or both, and brain levels of acetylcholine (ACh) were determined to elucidate possible mechanisms underlying adaptation to chronic cholinesterase (ChE) inhibition. In acutely treated animals, atropine had no effect on free ACh, but decreased bound ACh levels. Conversely, paraoxon increased both free and bound ACh. Atropine pretreatment totally prevented the paraoxon-induced rise in free and bound ACh. In chronically treated animals, atropine decreased total ACh content after the initial injection, with no further changes upon subsequent administration. ACh levels increased during the first three days of paraoxon treatment, but latter injections (days 4-7) did not produce further alterations. Daily pretreatment with atropine prevented the paroxon-induced increase in ACh levels on days 1-3, but could not prevent the paraoxon-induced rise in ACh on days 4-7. Results are discussed in terms of a possible neurotransmitter accumulation, occurring under conditions of chronic ChE inhibition, that may regulate the mobilization, storage, and release of ACh.
用阿托品、对氧磷或两者对大鼠进行急性（一天）和慢性（七天）处理，测定脑内乙酰胆碱（ACh）水平，以阐明慢性胆碱酯酶（ChE）抑制适应的潜在机制。在急性处理的动物中，阿托品对游离ACh无影响，但降低了结合ACh水平。相反，对氧磷增加了游离和结合ACh。阿托品预处理完全阻止了对氧磷诱导的游离和结合ACh升高。在慢性处理的动物中，阿托品在首次注射后降低了总ACh含量，后续给药无进一步变化。对氧磷处理的前三天ACh水平升高，但后期注射（第4 - 7天）未产生进一步变化。每天用阿托品预处理可防止对氧磷在第1 - 3天诱导的ACh水平升高，但不能防止对氧磷在第4 - 7天诱导的ACh升高。根据慢性ChE抑制条件下可能发生的神经递质积累来讨论结果，这种积累可能调节ACh的动员、储存和释放。
