Journal article: Proceedings of National Academy of Sciences of the USA

Risperidone and ritanserin but not haloperidol block effect of dizocilpine on the active allothetic place avoidance task

The article in PNAS was aimed at demonstrating if antipsychotics are primarily effective against cognitive deficit in an animal model of schizophrenia. Animal model of schizophrenia was induced by four daily administrations of MK-801 (a noncompetitive antagonist of N-methyl-D-aspartate receptors). Rats received antipsychotics risperidone (0.1 mg/kg and 1 mg/kg) or haloperidol (0.1. and 1 mg/kg) alone or in combination with MK-801. We measured cognitive abilities of rats by a new task called active allothetic place avoidance (AAPA), which was developed in the Department of Neurophysiology of Memory and Computational Neuroscience, Institute of Physiology ASCR.. Rats receiving risperidone or haloperidol alone exhibited impaired performance in AAPA task compared to controls. However, in animal model of schizophrenia (after administration of MK-801) risperidone but not haloperidol ameliorated MK-801-induced cognitive deficit. Risperidone has a different pharmacological profile than haloperidol. Risperidone shows affinity at serotonin-2A/2C (5-HT2A/2C) receptor. Next, we assessed antagonist of 5-HT2A/2C receptor (ritanserin) in rats with similar experimental schedule at doses 2.5 mg/kg and 5 mg/kg. Ritanserin did not impair cognitive function when given alone and ameliorated cognitive deficit in the animal model of schizophrenia. This beneficial effect of risperidone on cognitive deficit in animal model of schizophrenia is likely due to its action at 5-HT2A/2C receptors.
Bubenikova-Valesova V, Stuchlik A, Svoboda J, Bures J, Vales K. Risperidone and ritanserin but not haloperidol block effect of dizocilpine on the active allothetic place avoidance task, Proceedings of the National Academy of Sciences of the USA, 2008; 105 (3): 1061-1066 IF=9,6

Author: valesbiomed.cas.cz
          stuchlikbiomed.cas.cz
 

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