Latent inhibition (LI),

No abstract

Latent inhibition (LI) refers to retarded conditioning to a stimulus as a consequence of its non-reinforced pre- exposure. LI is impaired in some subsets of schizophrenic patients and in rats treated with amphetamine. Antipsychotic drugs (APDs) potentiate LI under conditions that are insufficient to produce LI in control animals, namely, low number of pre-exposures or high number of conditioning trials. The present experiments tested the proposition that LI potentiation under both conditions stems from the action of APDs in the conditioning stage. Experiments 1-3 used 10 pre-exposures and 2 conditioning trials, and tested the effects of 2.5, 5, and 10 mg/kg clozapine, respectively. Experiments 4-6 used 40 pre-exposures and 5 conditioning trials, with clozapine doses as above. Clozapine was administered in either the pre-exposure, the conditioning stage, or in both. In all the experiments, vehicle controls did not show LI. Overall, clozapine administration in conditioning, irrespective of drug condition in pre-exposure, produced LI. The implications of these results for the mechanism of action of antipsychotic drugs are discussed.

Latent inhibition (LI) refers to retarded conditioning to a stimulus as a consequence of its nonreinforced preexposure. LI is impaired in acute schizophrenic patients and in rats treated with amphetamine. Neuroleptic drugs enhance LI, and this effect is selective and specific for this class of drugs. The present experiments tested the proposition that neuroleptic-induced enhancement of LI stems from decreased capacity of stimulus-preexposed animals to switch responding according to the new stimulus-reinforcement contingency in the conditioning stage. LI was assessed using an off-baseline conditioned emotional response (CER) procedure in rats licking for water, consisting of three stages: preexposure to the-to-be conditioned stimulus, tone; conditioning, in which the preexposed stimulus was paired with a foot-shock; and test, in which LI was indexed by animals' degree of suppression of licking during tone presentation. Whereas in previous studies that demonstrated LI enhancement by neuroleptics, preexposure consisted of 10 to 40 tones, and conditioning included two tone-shock pairings, the present experiments used 40 tone preexposures, followed by an extended conditioning stage with five tone-shock pairings. It was expected that under these conditions no LI effect would be evident in untreated animals, but that animals treated with a neuroleptic drug, either during the entire LI procedure or only in conditioning, would show LI. Experiments 1 and 2 showed that LI was obtained in rats treated with haloperidol (0.1 mg/kg in experiment 1, 0.03 and 0.2 mg/kg in experiment 2) but not in the untreated controls. Experiment 3 showed that the same outcome was obtained when haloperidol (0.1 mg/kg) administration was confined to the conditioning stage. Experiment 4 showed that clozapine (5 mg/kg)-treated animals showed LI when the drug was confined to conditioning, but not to the preexposure stage. The implications of these results for the mechanism of action of neuroleptic drugs are discussed.

No abstract