Mice were treated with various doses of cycloheximide (CXM) 30 min prior to tests using a sequence of slowly repeated light flashes interrupted by a brief auditory stimulus. Both evoked and electroencephalographic (EEG) responses were recorded through chronic indwelling electrodes. The tests were repeated 24 hr later without additional drug treatments. Cycloheximide, especially in high doses, caused alterations in the brain electrical activity of mice. The alterations persisted for at least 24 hr after cycloheximide treatments. The time course of these effects did not correspond to the time course of cycloheximide effects on brain protein synthesis or polysome disaggregation. These results suggest that memory deficits often associated with the protein-synthesis inhibition by cycloheximide may be due, in part, to disturbances in the electrical activity of the brain. While not critical for learning or short-term memory, these electrical alterations may be related to neural mechanisms of long-term memory storage and retrieval.
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Antibiotic inhibitors of protein synthesis are able to disrupt long-term memory in experimental animals (Barondes and Cohen, 1966; Flexner and Flexner, 1969; Agranoff, 1968; Swanson et al., 1969; Andry and Luttges, 1972; Andry and Luttges, 1973). In general, these antibiotics have little direct The authors are grateful to J. Button for manuscript preparation and W. Bank for technical assistance. The work was supported, in part, by the University of Colorado Graduate School, CRCW.