Cholinergic blockade and response timing in rats.

The effects of central cholinergic blockade on the temporal regulation of behaviour were studied with a two-level DRL schedule. Five-month-old male Wistar rats had to press lever A and then wait for a minimum of 5 s before pressing lever B to obtain the reinforcer (sweetened milk). After a stable baseline performance, subjects were injected in random order with the general cholinergic blocker, scopolamine, 0.15 and 0.5 mg/kg, the peripheral cholinergic blocker, methylscopolamine, 0.15 and 0.5 mg/kg, and a combination of the cholinesterase inhibitor, physostigmine, 0.2 mg/kg, and scopolamine, 0.5 mg/kg. Each drug treatment was separated by 2 days of saline treatment. Results showed that scopolamine at 0.5 mg/kg significantly impaired the temporal regulation of the A-B response sequence: the median A-B inter-response time (IRT) was shortened and the coefficient of variation of the A-B IRT distribution was increased, thus revealing a loss in the sensitivity to time. This disruption of accurate timing behaviour lowered efficiency. The drug changed neither the duration of the B-A interval nor the A-B response rate, but significantly increased the rate of the superfluous B-B sequences. Methylscopolamine was without effects and physostigmine totally or partially reversed all the scopolamine effects. These results suggest that scopolamine at 0.5 mg/kg specifically affected the mechanism(s) underlying response timing, and that the effects were not secondary to changes in activity or motivation. They partly corroborate data obtained in other procedures and support the idea that the central cholinergic system is involved in the temporal regulation of behaviour.