Deletion of striatal adenosine A2A receptor spares latent inhibition and prepulse inhibition but impairs active avoidance learning
| Autor: | Catherine J. Wei, Philipp Singer, Detlev Boison, Benjamin K. Yee, Jiang-Fan Chen |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Receptor
Adenosine A2A Mice Transgenic Motor Activity Article Behavioral Neuroscience Glutamatergic Mice Latent inhibition Dopamine Conditioning Psychological medicine Avoidance Learning Animals Prepulse inhibition Homeodomain Proteins Analysis of Variance Sensory gating Learning Disabilities Dopaminergic Sensory Gating medicine.disease Corpus Striatum Reflex Acoustic Mice Inbred C57BL Inhibition Psychological medicine.anatomical_structure Schizophrenia Taste Taste aversion Psychology Neuroscience medicine.drug Psychoacoustics |
| Popis: | Following early clinical leads, the adenosine A(2A)R receptor (A(2A)R) has continued to attract attention as a potential novel target for treating schizophrenia, especially against the negative and cognitive symptoms of the disease because of A(2A)R's unique modulatory action over glutamatergic in addition to dopaminergic signaling. Through (i) the antagonistic interaction with the dopamine D(2) receptor, and (ii) the regulation of glutamate release and N-methyl-d-aspartate receptor function, striatal A(2A)R is ideally positioned to fine-tune the dopamine-glutamate balance, the disturbance of which is implicated in the pathophysiology of schizophrenia. However, the precise function of striatal A(2A)Rs in the regulation of schizophrenia-relevant behavior is poorly understood. Here, we tested the impact of conditional striatum-specific A(2A)R knockout (st-A(2A)R-KO) on latent inhibition (LI) and prepulse inhibition (PPI) - behavior that is tightly regulated by striatal dopamine and glutamate. These are two common cross-species translational tests for the assessment of selective attention and sensorimotor gating deficits reported in schizophrenia patients; and enhanced performance in these tests is associated with antipsychotic drug action. We found that neither LI nor PPI was significantly affected in st-A(2A)R-KO mice, although a deficit in active avoidance learning was identified in these animals. The latter phenotype, however, was not replicated in another form of aversive conditioning - namely, conditioned taste aversion. Hence, the present study shows that neither learned inattention (as measured by LI) nor sensory gating (as indexed by PPI) requires the integrity of striatal A(2A)Rs - a finding that may undermine the hypothesized importance of A(2A)R in the genesis and/or treatment of schizophrenia. |
| Databáze: | OpenAIRE |
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