From an animal model of an attentional deficit towards new insights into the pathophysiology of schizophrenia

The paper presents an animal model of schizophrenic-like attentional deficit, consisting of an inability to ignore irrelevant stimuli. It is based on the paradigm of latent inhibition (LI), in which animals learn to ignore repeatedly presented stimuli not followed by meaningful consequences. In a series of experiments it was demonstrated that the capacity to ignore irrelevant stimuli is lost in rats treated with systemic or intra-accumbens injections of amphetamine, in normal volunteers given amphetamine, in high "psychosis-prone" persons, in acute schizophrenic patients and in untreated male adult rats that were raised until weaning under conditions of extremely restricted stimulation. In addition, LI is lost following the disruption of the hippocampal input to the nucleus accumbens. In all of the above conditions tested for antagonism by anti-psychotic drugs a loss of LI is reversed. On the basis of these results we propose an animal model which accomodates a neurodevelopmental dysfunction, hippocampal pathology, mesolimbic DA overactivity, vulnerability to stress, and gender differences, all of which have been postulated as factors in the pathophysiology of schizophrenia.