Effects of haloperidol and pimozide on classical conditioning of the rabbit nictitating membrane response

Classical conditioning of the nictitating membrane response of the rabbit was accomplished by presenting tone and light conditioned stimuli for 800 msec before delivery of the unconditioned stimulus, consisting of a 100-msec electric shock to the skin over the paraorbital region of the head. Both haloperidol (250 microgram/kg i.v.) and an equimolar dose of pimozide (308 microgram/kg i.v.) significantly retarded the rate of acquisition of conditioned responses (CRs). Control experiments conducted with separate groups of rabbits indicated that the retardant effect of haloperidol on CR acquisition was not due to an effect on sensitization, pseudoconditioning, base-line responding or the unconditioned nictitating membrane reflex. In previously trained animals, haloperidol produced a significant (12.0 ob) elevation in the intensity threshold of a tone conditioned stimulus for elicitation of CRs. In a separate group of animals, and before any conditioning, haloperidol significantly blocked the amplitude and duration of a tone-induced facilitation of the nictitating membrane reflex. It was concluded that haloperidol blocks both the conditioned and unconditioned excitatory properties of a tone and this accounts for its ability to retard the rate of CR acquisition.