Temporal memory in mature and aged rats is sensitive to choline acetyltransferase inhibition

The effects of a potent inhibitor of choline acetyltransferase (ChAT), BW813U, on timing behavior in mature (6-10 months) and aged (26-30 months) male rats were assessed. Twenty rats were trained on a discrete trial 20-s peak-interval (PI) procedure. During baseline (non-drug) training, the time of the maximum response rate (peak time) for mature rats was approximately at the time of scheduled reinforcement, but peak time for aged rats was reliably later. A single administration of BW813U (100 mg/kg, ip) produced a long-lasting increase in peak time for both mature and aged rats that occurred gradually and was synergistic with age. These horizontal shifts in peak time indicate a change in the content of reference memory for the remembered time of reinforcement that is similar for both aging processes and BW813U administration. When a 5-s gap was imposed in the signal, PI-GAP procedure, control rats of both ages summed the signal durations before and after the gap, whereas rats given BW813U showed no retention of the signal duration prior to the gap. This loss of trial-specific temporal information suggests a drug-induced working memory dysfunction. Taken together, these results demonstrate that both working and reference memory for temporal information are sensitive to choline acetyltransferase inhibition in rats.