Schizophrenia Research Trends

Latent Inhibition and Learned Irrelevance Paradigms … 143phase. Applying the switching theory, this occurs as soon as the subject has switched fromthe CS-noUS to the CS-US association. MK-801 treated rats show persistent LI even after anumber of conditioning trials which disrupts LI in normal rats. This indicates that they arestill inhibited in expressing the CS-US association. In other words, NMDA antagonistsimpair the ability to switch between behaviors (53).The finding that glutamate depletion might be responsible for deficient behavioralswitching is in accordance with the theory proposing that NMDA receptor hypofunction isinvolved in the negative symptomatology of schizophrenia.LATENT INHIBITION IN HUMANSAnimal LI paradigms applied to humansOnly a few paradigms used to assess LI in animals can be directly transferred to humans.These are CTA and classical eyeblink conditioning. The CTA has been applied to humansusing cranberry juice as CS and apomorphine induced nausea as US (54;55). Eyeblinkconditioning studies investigating LI in humans have been conducted by several groups(35;56). The basic procedure for humans is the same as that applied to animals, but with aweaker corneal air puff.Additionally, there is also a modified human paradigm which applies conditionedsuppression (57). In this paradigm both the PE and the NPE subjects have to perform theTower of Toronto puzzle which requires the subjects to arrange four discs in a specific orderby translocating them over three vertical pegs. The task is repeated several times in order toachieve a problem-solving routine with constant times per move. After the training trials, thePE, but not the NPE group is preexposed to a pure tone (CS) while completing the puzzle.During the conditioning stage, the CS is paired with a loud burst of white noise (US) for bothgroups increasing the duration of the hand movement. The LI effect is measured by thedifferent degrees of suppression of ongoing motor activity (time per move) due to the noiseburst in the PE compared to the NPE group.Paradigms designed especially for human LI measurementsIn addition to paradigms adopted from animal LI testing procedures, there are some thatare designed specially for humans. These are Pavlovian conditioning of autonomic responses(58), instrumental learning to criterion (23;59), and the recently introduced visual LIparadigms (60-62).Pavlovian conditioning of autonomic responsesIn paradigms employing Pavlovian conditioning of autonomic responses, reactions of theautonomic nervous system are measured for LI assessment. The recorded variables are skin