Blockade of NMDA receptors located at the dorsomedial prefrontal cortex impairs spatial working memory in rats

WE investigated the effects of NMDA and muscarinic acetylcholine receptor blockade in the rostral part of dorsomedial (dmPFC) and dorsolateral prefrontal cortex (dlPFC) on spatial working memory (SWM) (delayed non-matching to position task (DNMTP)). The NMDA antagonist, CPP (0.01, 0.03, 0.1 and 0.3 mu g/hemisphere) and the muscarinic antagonist, scopolamine (10 mu g/hemisphere) were locally infused into the brain of male Wistar rats. In the mPFC CPP 0.1 mu g disrupted SWM delay-dependently and CPP 0.3 mu g caused a delay-independent performance deficit. Scopolamine disrupted non-cognitive performance, but did not affect SWM accuracy. In the dlPFC, scopolamine or lower doses of CPP did not affect SWM accuracy, but CPP 0.3 mu g disrupted non-cognitive performance. We concluded that the NMDA receptors in the dmPFC regulate SWM processes, whereas the muscarinic receptors in the dmPFC mediate non-cognitive performance in the DNMTP task. (C) 1999 Lippincott Williams & Wilkins.