Atypical antipsychotics ameliorates learning impairments of N-methyl-D-aspartate receptor (NMDAR) antagonism during acquisition of an operant conditioning task

RAPANELLI M; FRICK LUCIANA ROMINA; BERNARDEZ M; ZANUTTO BS

Washington

Congreso; Annual Meeting of the Society for Neuroscience; 2011

SfN - Society for Neuroscience

N-methyl-D-aspartate receptor (NMDAR) plays a critical role in learning and memory. Besides, it has been shown that administration of NMDAR antagonists like ketamine, Mk801 or phenylciclidine in rodents mimics the negative symptoms of schizophrenia. Although, there is evidence of the cognitive impairments that NMDAR antagonist administration produces in animals, most of the research performed until the present has been related to working memory tasks. Here, we studied the effects of Mk801 administration and treatment with atypical antipsychotics during learning a reward dependent task like the operant conditioning. First, we found that rats injected with Mk801 (0.1mg/kg) showed a diminished performance in the first (p<0.01) and second (p<0.001) session with respect to control group. Next, we found that risperidone (1mg/kg) totally impaired learning where animals reached a maximum of 11% of responses during training procedures. Then, administration of buspirone (10 mg/kg) during learning resulted in a detrimental effect in the performance only in the first session (p<0.05) with respect to the control group. Finally, we found that concomitant administration of buspirone or risperidone together with Mk801 totally ameliorated the negative effects of Mk801 returning performance values to control group. These results shows that NMDAR antagonist Mk801 impaired learning of a reward dependent task and that administration of risperidone and buspirone ameliorate the cognitive impairments. This study brings more insight into the interaction of glutamatergic and serotoninergic circuits in the negative symptoms produced by NMDAR antagonism.