Schizophrenia Research Trends

Latent Inhibition and Learned Irrelevance Paradigms … 139can almost be excluded from being responsible for LI disruption, i.e. faster learningfollowing preexposure (19;21).Another advantageous property of LI is that it can be similarly demonstrated in humansand animals. Actually, LI was first studied in animals of different species (for a review see(22)) and then translated to paradigms which could be performed in humans (23). There areonly a few paradigms which can be used in both animals and humans. Such paradigms thatcan be applied to various species are very useful because the effects of manipulations (e.g.pharmacological, physiological, environmental) can be compared across species and maygive clues to elementary questions. Experiments with rats and mice especially allow one toanalyze the neural and neurochemical basis of LI and have provided evidence for the centralelements in the pathophysiology of schizophrenia (24-28). A thorough investigation ofhuman LI data has led to the conclusion that LI is the same phenomenon in humans andanimals, and that the processes underlying LI are analogous across species (17).How to test LI – the basic procedureClassical conditioning, also referred to as Pavlovian conditioning, involves learningabout the association of two or more stimuli. In a conditioning procedure, the pairedpresentation of a CS and US leads to a CS-US association in which the CS becomes a signalfor the US. Latent inhibition refers to a CS-preexposure effect which results from the nonreinforcedpresentation of the CS alone prior to the conditioning procedure (Fig. 1). All LItest paradigms share a basic procedure (28) involving two or three distinct stages:preexposure, conditioning and, in some paradimgs, a test phase. As all animal and mosthuman LI paradigms apply a between-subject design, two groups, a “stimulus preexposed”(PE) and a “non-preexposed” (NPE) group, are formed. At the preexposure stage, subjects inthe PE group are repeatedly exposed to the CS, which is not followed by any consequences,while subjects in the NPE group do not encounter the CS. When preexposure is completed,all subjects enter into the conditioning stage in which the CS is paired with a reinforcer (US)over a number of trials. The resulting conditioned response (CR), i.e. the rate of conditioning,is quantified either during the conditioning stage, or in a separate test phase in which the CSis presented alone. The LI effect is measured by comparing the performance of the PE to thatof the NPE group.Animal LI test paradigmsLATENT INHIBITION IN ANIMALSThere are three test paradigms commonly used to assess LI in rats and mice. These areconditioned taste aversion (CTA), conditioned emotional response (CER) and two-way activeavoidance. Classical eyeblink conditioning is a further paradigm that has a long history oftesting the neural substrates of LI and which is predominantly applied to rabbits.