Pilocarpine administered in doses of 1.25-10.0 mg/kg (IP) produced a variety of mouth movements in the rat. The most frequent of these movements was a chewing behaviour, which increased up to a mean frequency of over 40 per min at the highest doses. Tongue protrusion and gaping also showed dose-dependent increases. Yawning tended to increase in some doses, though these increases were not significant, and yawning was relatively infrequent. Pre-treatment with scopolamine reduced these responses, while pre-treatment with methyl scopolamine did not. Injections of oxotremorine or arecoline, but not carbachol, produced dose-related increases in mouth movements similar to those produced by pilocarpine. These results suggest that mouth movements in the rat are caused by stimulation of central muscarinic receptors. This may prove to be an important behavioural sign of central cholinomimetic activity.

Four experiments compared the CNS effects of a novel M1/M3 receptor agonist L-689,660 with those of the M1/M3 muscarinic receptor agonist AF102B. In the mouse tail-flick test of antinociception (TF) the minimum effective doses to increase tail-flick latency (MED) of L-689,660 and AF102B were 0.03 mg/kg and 10.0 mg/kg, respectively. In a rat conditioned-suppression-of-drinking (CSD) test of reference memory, doses of 0.3 and 1.0 mg/kg L-689,660 and a dose of 5.0 mg/kg AF102B reversed a scopolamine-induced deficit in performance (0.6 mg/kg). Although there was a tendency for L-689,660 to reverse the scopolamine-induced (0.4 mg/kg) performance deficit in a rat delayed-matching-to-position (DMTP) test, the difference failed to reach statistical significance. In contrast, a 5.0 mg/kg dose of AF102B potentiated the scopolamine-induced deficit in choice accuracy and the number of trials completed on this task. In a response sensitivity (RS) test, chain-pulling rates were significantly decreased by L-689,660 (MED = 0.03 mg/kg) and by AF102B (MED = 5.0 mg/kg). These results suggest that L-689,660 and AF102B may ameliorate or reverse a scopolamine-induced deficit, but only at doses that also reduce chain-pulling rates on operant schedules of reinforcement.