D1 receptor modulation of hippocampal-prefrontal cortical circuits integrating spatial memory with executive...

Dopamine (DA) within the prefrontal cortex (PFC) plays an important role in modulating the short-term retention of information during working memory tasks. In contrast, little is known about the role of DA in modulating other executive aspects of working memory such as the use of short-term memory to guide action. The present study examined the effects of D1 and D2 receptor blockade in the PFC on foraging by rats on a radial arm maze under two task conditions: (1) a delayed task in which spatial information acquired during a training phase was used 30 min later to guide prospective responses, and (2) a nondelayed task that was identical to the test phase of the delayed task but lacked a training phase, thereby depriving rats of previous information about the location of food on the maze. In experiment 1, microinjections of the D1 antagonist SCH-23390 (0.05, 0.5, or 5 microg/µl), but not the D2 antagonist sulpiride (0.05, 0.5, or 5 microg/microl), into the prelimbic region of the PFC before the test phase disrupted performance of the delayed task without affecting response latencies. In contrast, neither drug affected performance of the nondelayed task. In the present study, we also investigated the role of D1 receptors in modulating activity in hippocampal-PFC circuits during delayed responding. Unilateral injections of SCH-23390 into the PFC in the hemisphere contralateral to a microinjection of lidocaine into the hippocampus severely disrupted performance of the delayed task. Thus, the ability to use previously acquired spatial information to guide responding 30 min later on a radial arm maze requires D1 receptor activation in the PFC and D1 receptor modulation of hippocampal inputs to the PFC. These data suggest that D1 receptors in the PFC are involved in working memory processes other than just the short-term active retention of information and also provide direct evidence for DA modulation of limbic-PFC circuits during behavior.