Effects of lobeline, a nicotinic receptor agonist, on learning and memory

The effects of (-)-lobeline were assessed in two learning and memory tasks in which nicotine-induced enhancement of performance has previously been demonstrated. Lobeline (19 mumol/kg, IP) administered immediately after inhibitory (passive) avoidance training improved retention performance assessed 24 h later, as rats that received this dose of lobeline took significantly longer to enter the shock compartment on the test day than rats that had been treated with vehicle. Pretraining lobeline treatment (1.9 mumol/kg, IP) significantly improved performance of rats with septal lesions in a spatial discrimination water maze, a finding confirmed when rats were retrained using new spatial locations and vehicle and lobeline treatments were reversed in a crossover design. The effective dose of lobeline in the inhibitory avoidance task was about 10-fold higher than that generally reported for nicotine, and direct comparison of the suppression of locomotor activity shortly after administration of nicotine or lobeline also revealed a 10-fold greater potency for nicotine. In contrast, no difference was found between the effective dose of lobeline in the current study and that we previously found with nicotine in the water maze. These findings suggest that lobeline's effects on the performance of learning and memory tasks may be similar to those of nicotine. Coupled with previous reports that lobeline does not produce the nicotine cue in drug discrimination experiments, this study also suggests that nicotinic receptors involved in the modulation of memory processes may be distinct from those involved in producing the nicotine cue.