The pharmacology of latent inhibition as an animal model of schizophrenia.
The nature of the primary symptoms of schizophrenia and our lack of knowledge of its underlying cause both contribute to the difficulty of generating convincing animal models of schizophrenia. A more recent approach to investigating the biological basis of schizophrenia has been to use information processing models of the disease to link psychotic phenomena to their neural basis. Schizophrenics are impaired in a number of experimental cognitive tasks that support this approach, including sensory gating tasks and models of selective attention such as latent inhibition (LI). LI refers to a process 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 that characterise acute schizophrenia. Several claims have been made for LI having face and construct validity for schizophrenia. In this review of the pharmacological studies carried out with LI we examine its claim to predictive validity and the role of methodological considerations in drug effects. The data reviewed demonstrate that facilitation of low levels of LI is strongly related to demonstrated antipsychotic activity in man and all major antipsychotic drugs, both typical and atypical, have been shown to potentiate LI using a variety of protocols. Very few compounds without antipsychotic activity are active in this model. In contrast, disruption of LI occurs with a wide range of drugs and the relationship with psychotomimetic potential is less clear. Although reversal of disrupted LI has also been used as a model for antipsychotic acticity, mostly using amphetamine-induced disruption, insufficient studies have been carried out to evaluate its claim to predictive validity. However, like facilitation, it is sensitive to both typical and atypical antipsychotic agents. The data we have reviewed here demonstrate that facilitation of LI and, perhaps to a lesser extent, reversal of disrupted LI fulfil the criteria for predictive validity.
Moser
P C
PC
Sanofi-Synthélabo, 31 Av. P.V. Couturier, 92225 Cédex, Bagneux, France. paul.moser@sanofi-synthelabo.com
Hitchcock
J M
JM
Lister
S
S
Moran
P M
PM
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001288:Attention / Q000187:drug effects*; D006801:Humans; D013216:Reflex, Startle / Q000187:drug effects*; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents