Effect of two inhibitors of dopamine beta-hydroxylase on maturation of memory in mice.

Bitemporal injections of puromycin that primarily affect the hippocampal-enthorhinal cortical areas suppress memory of maze-learning in mice for 3 days after training but are ineffective 6 or more days after training. At these later times, injections affecting widespread areas of the brain in addition to the hippocampal-entorhinal area are necessary for amnesia. These observations are interpreted to indicate that the locus of the memory trace has enlarged at 6 days to include other parts of the central nervous system in addition to the hippocampal-entorhinal area. To produce an imbalance of neurotransmitters and so to test their importance in enlargement of the memory trace's locus, we treated mice for 7 days after training with inhibitors of dopamine beta-hydroxylase. These mice, unlike untreated controls, developed amnesia after bitemporal injections of puromycin. In view of additional control experiments, we interpret these results to suggest that an imbalance of transmitters suppresses the normal enlargement of the locus of the memory trace.