Galantamine facilitates acquisition of a trace-conditioned eyeblink response in healthy, young rabbits

Abstract

Previous work has demonstrated that drugs increasing brain concentrations of acetylcholine can enhance cognition in aging and brain-damaged organisms. The present study assessed whether galantamine (GAL), an allosteric modulator of nicotinic cholinergic receptors and weak acetylcholinesterase inhibitor, could improve acquisition and retention of an eyeblink (EB) classical conditioning task in healthy, young animals. We trained 24 rabbits (n = 8/group) in a 1000-msec trace Pavlovian EB conditioning paradigm in which a tone conditioned stimulus (CS) was presented for 500 msec, followed by a 500-msec trace period in which no stimuli were presented. A 100-msec corneal airpuff was the unconditioned stimulus (US). Acquisition sessions, consisting of 100 trials each, occurred daily for 10 consecutive days, followed by 3 d of extinction training. Animals were treated with one of three doses of GAL (0.0-3.0 mg/kg) prior to each session. Animals that received 3.0 mg/kg GAL showed significantly more EB conditioned responses (CRs) in fewer training trials than animals receiving either 1.5 mg/kg GAL or vehicle injections. GAL had no effect on CR performance during extinction. Pseudoconditioning control experiments, consisting of 200 explicitly unpaired tone-puff presentations indicated that GAL did not increase reactivity to the CS or US. These findings indicate that GAL may improve acquisition of moderately difficult associative learning tasks in healthy young organisms.

Figure 1

Effects of three doses of galanthamine (GAL; as indicated) on acquisition and extinction of conditioned eyeblink (EB) responses (CRs) in a trace-conditioning paradigm. The acquisition data represent the percent EB CRs during each 100-trial session during which a 500-msec, 1000-Hz, 75-db (SPL) tone-conditioned stimulus (CS) was presented 500 msec prior to a 100-msec, 3-ψ corneal airpuff unconditioned stimulus on each trial. During extinction, 100 CS-alone trials were presented.

Figure 2

(A) Eyeblink conditioned response (EB CR) probability during the first 10 trials of session 1 for groups of rabbits that received different doses of galanthamine hydrobromide as shown. (B) Mean number of eyeblink conditioned responses (CRs) as a function of blocks of 10 trials each during the first session of trace classical conditioning. Data are shown for three groups of eight rabbits each that received different doses of galanthamine hydrobromide as shown.

Figure 3

Effects of three doses of galanthamine (as indicated) on CR and UR amplitude (A) and latency (B) during trace eyeblink classical conditioning training and extinction. Each acquisition session consisted of 100 CS/US presentations, and each extinction session consisted of 100 CS presentations without the US occurring.

Figure 4

Effects of 3 mg/kg galanthamine or vehicle on eyeblink response amplitude and latency to unpaired tone and airpuffs presented in a pseudorandom sequence over 13 d. (A) Effects of galantamine on CR amplitude during pseudoconditioning. (B) Effects of galantamine on CR latency during pseudoconditioning. A total of 100 presentations of each stimulus was presented on each day.

Figure 5

Effects of three doses of galanthamine (as indicated) on body weight over 13 d of training. Analyses indicated significant weight increases for all rabbits, with no significant group differences.