Stimulation of dopamine D1 receptors in the avian fronto-striatal system adjusts daily cognitive fluctuations

Several studies have shown that the level of dopaminergic transmission and D1 receptor signaling is crucial for working memory (WM) in the prefrontal cortex (PFC) of mammals. Thus, hyper- or hypostimulation of prefrontal D1 receptors are pathophysiological findings often involved in cognitive and WM impairments. These observations can be mimicked by supranormal stimulation or inhibition with D1 receptor agonists or D1 antagonists, respectively. As a consequence, it is assumed that there is a normal range of dopamine function in prefrontal cortex that can be described as an inverted U-shaped relationship between dopamine transmission, i.e. D1 receptor stimulation, and intact WM. If this is true, short-term fluctuations of cognitive performance might be described as small-scale adjustments along the tip of the inverted U-curve and should depend on D1 receptor stimulation. We tested this hypothesis in pigeons performing a delayed-matching-to-sample task (DMTS), a classic paradigm to test WM. We applied the D1 agonist SKF81297 and the D1 antagonist SCH23390 into the nidopallium caudolaterale (NCL), the avian functional analogue of the PFC, and simultaneously in the medial striatum (MSt), by in vivo microdialysis while the animals performed the task. Animals showed daily fluctuations in WM performance. While the D1 agonist was able to improve or to decrease performance during low or strong performance periods, respectively, performance did not differ from control with the D1 antagonist. This study shows that D1 receptors seem to calibrate differentially prefronto-striatal functions based on individual low or high performance states.