The pharmacology of latent inhibition as an animal model of schizophrenia

The nature of the primary symptoms of schizophrenia and our lack of knowled ge of its underlying cause both contribute to the difficulty of generating convincing animal models of schizophrenia. A more recent approach to invest igating the biological basis of schizophrenia has been to use information p rocessing models of the disease to link psychotic phenomena to their neural basis. Schizophrenics are impaired in a number of experimental cognitive t asks that support this approach, including sensory gating tasks and models of selective attention such as latent inhibition (LI). LI refers to a proce ss in which noncontingent presentation of a stimulus attenuates its ability to enter into subsequent associations, and it has received much attention because it is widely considered to relate to the cognitive abnormalities th at characterise acute schizophrenia. Several claims have been made for LI h aving face and construct validity for schizophrenia. In this review of the pharmacological studies carried out with LI we examine its claim to predict ive validity and the role of methodological considerations in drug effects. The data reviewed demonstrate that facilitation of low levels of LI is str ongly related to demonstrated atitipsychotic activity in man and all major antipsychotic drugs, both typical and atypical, have been shown to potentia te LI using a variety of protocols. Very few compounds without antipsychoti c activity are active in this model. in contrast, disruption of LI occurs w ith a wide range of drugs and the relationship with psychotomimetic potenti al is less clear. Although reversal of disrupted LI has also been used as a model fur antipsychotic activity, mostly using amphetamine-induced disrupt ion, insufficient studies have been carried out to evaluate its claim to pr edictive validity. However, like facilitation, it is sensitive to both typi cal and atypical antipsychotic agents. The data we have reviewed here demon strate that facilitation of LI and, perhaps to a lesser extent, reversal of disrupted LI fulfil the criteria for predictive validity. (C) 2000 Elsevie r Science B.V. All rights reserved.