Behavioural effects of the nicotinic agonists N-(3-pyridylmethyl)pyrrolidine and isoarecolone in rats

The nicotinic agonists N-(3-pyridylmethyl)pyrrolidine (PMP) and isoarecolone have been compared with (–)-nicotine in three behavioural procedures and as inhibitors of [³H]-(–)-nicotine binding. Locomotor activity was recorded as movements between beams of infra-red light (ambulation). In experimentally naive rats, nicotine, PMP and isoarecolone reduced ambulation. In rats receiving nicotine chronically and previously exposed to the activity cages, nicotine and PMP increased ambulation in a dose-related manner. However, isoarecolone did not increase ambulation at doses that were active in other procedures. In rats trained to discriminate nicotine from saline in a two-bar operant conditioning procedure with food reinforcement, there was full generalization to PMP. It was also found that PMP potently inhibited the binding of [³H]-(–)-nicotine to rat brain membranes in vitro. These results were discussed with previous data for the discriminative stimulus and ligand-binding effects of isoarecolone obtained under similar conditions. The relative potency of PMP in different behavioural procedures was similar to that of (–)-nicotine. However, isoarecolone was relatively 10 times more potent in decreasing ambulation than would have been expected from its potency in the ligand-binding and discriminative stimulus procedures. The results suggest that the pharmacodynamic action of isoarecolone differs from that of nicotine and PMP, and that it will be a useful probe in further analyses of central nicotinic mechanisms.