P0167 - The effect of mGluR I and II agonist on cognitive deficit in animal model of psychosis-like behavior

Abstract

One of the major arguments that glutamatergic system may be disrupted in schizophrenia represents fact that antagonists of the NMDA receptor impairs cognitive function in healthy volunteers in a manner that is very similar to the cognitive deficit observe in patients with schizophrenia. Consequently application of NMDA antagonists were established as an animal model of schizophrenia

NMDA receptors are present by nearly all subtypes of neurons, and that is why direct pharmacological manipulation of this group of receptors may produce a global disruption in brain function and produce profound side effects. Hence indirect modulation of glutamatergic transmission by metabotropic glutamate receptors (mGluR) is numbered among promising approaches.

Testing the cognitive abilities of animals with experimentally induced psychotomimetic state requires specific behavioral paradigms, which should have a high cognitive demand for their efficient solution. For that reason we used test active alothetic place avoidance (AAPA). This spatial task is suitable for detection of attention and information processing.

Application of NMDA antagonist MK-801 (0.1 mg/kg) leads to slight cognitive deficit without changes in locomotion. We investigated effect of ACPD (agonist of mGluR group I and II) in doses 0.01 mg/kg a 0.1 mg/kg. Administration of ACPD alone did not influence locomotor activity and cognitive parameters. ACPD significantly improved performance of AAPA task after MK-801. Studied drug even reduced massive cognitive disturbances and hyperlocomotion after MK-801. Our results show that agonists of mGluR I and II could enhanced cognitive function in patient with schizophrenia. Project was supported by IGA MZCR NR/9178-3; MSMT 1M0517.