Nicotinic cholinergic system involvement in eyeblink classical conditioning in rabbits

A nicotinic cholinergic antagonist, mecamylamine (MEC), was administered to rabbits tested on eyeblink classical conditioning (EBCC) in the 750-ms delay paradigm for 10 90-trial sessions. Nicotinic receptors were measured in 3 brain regions in 5 treatment groups: paired conditioned stimulus-unconditioned stimulus (CS-US) presentations with (a) vehicle, young; (b) vehicle, older; (c) 0.5 mg/kg MEC, young; unpaired CS-US with (d) 0.5 mg/kg MEC, young; and (e) vehicle, young. Daily MEC injections disrupted acquisition in young rabbits (769 trials to learning criterion vs. 323 trials for vehicle-treated young rabbits). MEC-treated young rabbits learned similarly to older rabbits. Brain nicotinic receptors were not affected by 10 daily MEC injections. To our knowledge, this experimental protocol, using a low MEC dose to selectively inhibit nicotinic cholinergic receptors, is the first to demonstrate a role for nicotinic cholinergic receptors in EBCC.