Synergistic interaction of dopamine D1 and glutamate N-methyl-d-aspartate receptors in the rat dorsal striatum controls attention

Abstract

The balance between corticostriatal glutamate inputs and mesostriatal dopamine afferents converging onto the same postsynaptic spines of striatal medium spiny neurons in the dorsal striatum is believed to be crucial for regulating executive functions including attention.In the present study we examined the role of dopamine D(1) and glutamate N-methyl-d-aspartate (NMDA) receptors within the medial territory of the dorsal striatum (dm-STR) of the rat during performance of a selective attention task such as the 5-choice serial reaction time (5-CSRT) task, which incorporates a variety of measures including accuracy of visual discrimination (an index of attentional functioning), omissions, premature and perseverative responses (indices of inhibitory response control) and correct response latency (decision time). Infusion of 30 ng/side of the competitive NMDA receptor antagonist 3-(R)-2-carboxypiperazin-4-propyl-1-phosphonic acid (CPP) in the dm-STR decreased accuracy and increased the proportion of omission but had no effect on premature or perseverative responding or correct response latency. A lower dose of 10 ng/side CPP only affected omissions. Blockade of D(1) receptors in the dm-STR by SCH23390 (50 and 100 ng/side) had no effect on accuracy but at 100 ng/side SCH23390 decreased anticipatory responding and increased the proportion of omissions. Co-infusion of SCH23390 (50 ng/side) and CPP (10 ng/side), at individually ineffective doses, potently reduced the accuracy of visual discrimination. The effects were highly selective as no changes in response control, decision time and omissions were detected. The data suggest that the synergistic interaction of D(1) and NMDA receptors on the dendritic spines of GABA neurons within the dm-STR may represent a mechanism for the control of attention.