Scopolamine disruption of behavioral and hippocampal responses in appetitive trace classical conditioning

Twelve young rabbits (3-6 months; Oryctolagus cuniculus) were classically conditioned in a trace jaw movement paradigm (300 ms tone, 450 ms trace, 200 ms intraoral water) after implantation of electrodes into area CA1 of dorsal hippocampus. Rabbits were divided into two groups and administered either 0.5 mg/kg scopolamine hydrobromide (HBr) or 0.5 mg/kg scopolamine methylbromide (MBr) subcutaneously before daily training sessions. Rabbits given HBr took significantly more trials to reach a behavioral criterion of eight conditioned responses in any nine consecutive trials than rabbits given MBr (P = 0.03). Conditioned, but not unconditioned, rhythmic jaw movement responses of the HBr group were of a lower frequency (Hz) than those of MBr rabbits (P = 0.02). The magnitude of hippocampal conditioning-related responses across the first 3 days of training was significantly smaller for HBr rabbits than for MBr rabbits (P = 0.02). These effects of central cholinergic blockade are similar to those reported for undrugged aging rabbits trained in the same paradigm (Seager MA, Borgnis RL, Berry SD. Neurobiol. Aging 1997;18(6):631 639).