Clozapine does not alleviate cognitive deficit following MK-801 administration in the Active Allothetic Place Avoidance (AAPA) task but it suppresses hyperlocomotion

A. Stuchlík¹, V. Bubeníková² and K. Valeš¹

¹Institute of Physiology, Academy of Sciences, Prague, Czech republic
²Prague Psychiatric Center, Prague, Czech Republic

Administration of non-competitive NMDA receptor antagonists is considered as an animal model of schizophrenia. Blockade of brain NMDA receptors with MK-801 results in specific behavioural alterations, including hyperlocomotion, stereotypies, social deficit and impaired sensorimotor gating. These changes can be ameliorated by application of antipsychotics. Nonetheless, the effect of atypical antipsychotics on the cognitive de.cit following MK-801 application is not elucidated yet. The prezent study tested whether clozapine will alleviate the cognitive deficit following administration of two doses of MK-801 (0.1 a 0.3 mg/kg, s.c.).in the Active Allothetic Place Avoidance (AAPA) task.

In this task, rats are required to avoid a room-frame fixed shock sector on the continuously rotating arena, and this task requires the rats to separate spatial stimuli into coherent representations and use only the room-frame system for the efficient navigation.

The results showed that application of MK-801 increases locomotor activity and decrease spatial efficiency, measured as the increased number of shock sector entrances and decreased maximum time avoided. Clozapine decreased total distance walked in the session but it was ineffective in alleviating decreased spatial efficiency following MK-801. It is summed up that in the AAPA task, clozapine is capable of decreasing hyperlocomotion but incapable of alleviating deficits in spatial cognition.

The work was suported by grants MZ ÈR-NL-7684-3, GACR No . 309/03/P126 and GACR No 309/03/0715 and by MSMT CR project 1M0002375201.

Paper presented at Measuring Behavior 2005 , 5^th International Conference on Methods and Techniques in Behavioral Research, 30 August - 2 September 2005, Wageningen, The Netherlands.

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