Memory impairment during prolonged training in mice given inhibitors of cerebral protein synthesis

Abstract

When mice were given prolonged discrimination training to escape shock in an automated apparatus shortly after subcutaneous administration of the protein synthesis inhibitor cycloheximide (CXM), acquisition was normal during the initial (15–21) trials. Beyond this point, however, mice given CXM did not continue to improve as rapidly as mice given saline. Similar results were found when training occurred 4 h after intracerebral injection of CXM or puromycin. In contrast, isoCXM which depresses activity like CXM but does not inhibit cerebral protein synthesis had no effect on acquisition. Studies of the effects of different doses of CXM on activity, cerebral protein synthesis, the acquisition effect, and memory 24 h after brief training tended to associate the acquisition effect with inhibition of cerebral protein synthesis rather than to side effects of CXM. The results suggest that impairment in learning observed a few minutes after the beginning of prolonged training is due to inhibition of protein synthesis. Expression of normal memory may depend on cerebral protein synthesis within minutes after the beginning of training.