Experimental Manipulation of Acetylcholine Levels in Developing Rat Brain: Neurochemistry and Behavior

An attempt was made to manipulate experimentally the acetylcholine (ACh) system during rapid development of the rat brain. Developmental periods of ACh manipulated were 2 to 15 days and 15 to 28 days postnatally. The findings showed that the highest level of drug manipulation .75 mg/kg physostigmine and, .025 mg/kg methscopolamine significantly produced the highest level of ACh, lowest activity levels of both acetylcholinesterase (AChE) and choline acetyltransferease (ChAc) as compared to the intermediate, and control doses. This dose-response relationship was obtained in the animals injected over a 15- to 28-day period during the period of maximal growth of the acetylcholine system. These statistically significant differences measured at 24 hr. after injection support the thesis that injections during the critical period of development produce longer lasting effects than if administered at other periods. Behavioral measures, GO:NO-GO discrimination avoidance tasks, were also both significantly related to the highest dose group yet were not differentiated to developmental periods of injections.