In view of the evidence that cognitive deficits in
schizophrenia are critically important for long-term outcome, it is essential to establish the effects that the various
antipsychotic compounds have on cognition, particularly second-generation drugs. This parallel group, placebo-controlled study aimed to compare the effects in healthy volunteers (n = 128) of acute doses of the atypical
antipsychotics amisulpride (300 mg) and
risperidone (3 mg) to those of
chlorpromazine (100 mg) on tests thought relevant to the schizophrenic process: auditory and visual latent inhibition, prepulse inhibition of the acoustic startle response, executive function and eye movements. The drugs tested were not found to affect auditory latent inhibition, prepulse inhibition or executive functioning as measured by the Cambridge Neuropsychological Test Battery and the FAS test of verbal fluency. However,
risperidone disrupted and
amisulpride showed a trend to disrupt visual latent inhibition. Although
amisulpride did not affect eye movements, both
risperidone and
chlorpromazine decreased peak saccadic velocity and increased antisaccade error rates, which, in the
risperidone group, correlated with
drug-induced akathisia. It was concluded that single doses of these drugs appear to have little effect on cognition, but may affect eye movement parameters in accordance with the amount of sedation and
akathisia they produce. The effect
risperidone had on latent inhibition is likely to relate to its serotonergic properties. Furthermore, as the trend for disrupted visual latent inhibition following
amisulpride was similar in nature to that which would be expected with
amphetamine, it was concluded that its behaviour in this model is consistent with its preferential presynaptic
dopamine antagonistic activity in low dose and its efficacy in the negative symptoms of
schizophrenia.