The effects of anticholinergic drugs on delayed time discrimination performance in rats

To investigate the effects of the muscarinic antagonist scopolamine and the nicotinic antagonist mecamylamine on time discrimination and short-term memory, rats were trained on a delayed conditional time discrimination task until performance stabilized. In a two-lever operant chamber, pressing one lever was correct after the presentation of a stimulus light for 2 seconds (SD short); and pressing the other lever was correct after presentation of a stimulus light for 8 seconds (SD long). Scopolamine (0.06 mg, 0.25 mg, and 1.0 mg/kg) attenuated performance in a dose-dependent manner. Furthermore, the drug decreased nose-pokes (an activity necessary to trigger the presentation of the discriminative stimuli and the presentation of the response levers), and increased response delay (time from opportunity to lever press to actual lever press). Performance attenuating effects of mecamylamine in the time discrimination task did not appear unless high doses (8 mg/kg) of the drug were given. With increasing delays between 0 and 8 seconds, animals injected with saline developed a bias towards reporting the occurrence of the SD long, independent of the actual stimulus presented. A reversal of this bias was seen in animals injected with scopolamine; they more often reported the occurrence of the SD short. Our results support a role for muscarinic receptors in discrimination learning, attention, and time estimation.