The effect of the beta-adrenergic receptor antagonist, propranolol, on the cerebral spread of a memory trace in mice.

Bi-temporal injections of puromycin that primarily affect the hippocampal-entorhinal areas consistently induce amnesia of aversive maze-learning in mice for 3 days after training but are consistently ineffective if given 6 or more days after training. At these later times, additional puromycin sites covering widespread areas of the forebrain are necessary to induce amnesia. Consistent with other evidence, these observations are interpreted to indicate that the locus of the memory trace becomes more widespread during the 6-day period. A single subcutaneous injection of (-)-propranolol (50 micrograms/kg) given either before or 2 days after training suppressed engram spread for 60-90 days, at which time engram spread spontaneously occurred. This effect of propranolol was stereospecific. Suppression of engram spread persisted for a prolonged period in spite of the rapid recovery (about 4 hr), following treatment, of the normal level of specific binding of 3H-dihydroalprenolol in membrane preparations of the cerebral hemispheres and of 125I-pindolol in selected areas of the forebrain, diencephalon and brainstem.