The differential effects of chlorpromazine and haloperidol on latent inhibition in healthy volunteers

Latent inhibition (LI) is a measure of reduced learning about a stimulus to which there has; been prior exposure without any consequence. It therefore requires a comparison between a pre-exposed (PE) and a non-pre-exposed (NP E) condition. Since, in animals, LI is disrupted by amphetamines and enhanc ed by antipsychotics, LI disruption has been proposed as a measure of the c haracteristic attentional deficit in schizophrenia: the inability to ignore irrelevant stimuli. The findings in humans are, however, inconsistent. In particular, a recent investigation suggested that since haloperidol disrupt ed LI in healthy volunteers, and LI was normal in non-medicated patients wi th schizophrenia, the previous findings in schizophrenic patients were enti rely due to the negative effects of their medication on LI (Williams et al. , 1998). We conducted two studies of antipsychotic drug effects on auditory LI using a within-subject, parallel group design in healthy volunteers. In the first of these, single doses of haloperidol (1 mg. i.v.) were compared with paroxetine (20 mg p.o.) and placebo, and in the second, chlorpromazin e (100 mg p.o.) was compared with lorazepam (2 mg. p.o.) and placebo. Eye m ovements, neuropsychological test performance (spatial working memory (SWM) , Tower of London and intra/extra dimensional shift, from the CANTAB test b attery) and visual analogue rating scales,were also included as other measu res of attention and frontal lobe function. Haloperidol was associated with a non-significant reduction in LI scores, and dysphoria/akathisia (Barnes Akathisia Rating Scale) in three-quarters of the subjects. The LI finding m ay be explained by increased distractibility which was indicated by an incr ease in antisaccade directional errors in this group. In contrast, LI was s ignificantly increased by chlorpromazine but not by an equally sedative dos e of lorazepam (both drugs causing marked decreases in peak saccadic veloci ty). Paroxetine had no effect on LT, eye movements or CANTAB neuropsycholog ical test performance. Haloperidol was associated with impaired SWM, which correlated with the degree of dysphoria/akathisia, but no other drug effect s on CANTAB measures were detected. We conclude that the effect of antipsyc hotics on LI is both modality and pharmacologically dependent and that furt her research using a wider range of antipsychotic compounds is necessary to clarify the cognitive effects of these drugs, and to determine whether the re are important differences between them.