Effects of local application of dopaminergic drugs into the dorsal part of the medial prefrontal cortex of rats in a delayed matching to position task: comparison with local cholinergic blockade.

ABSTRACT

Lesions of the medial prefrontal cortex (mPFC) disrupt performance in a variety of delay tasks, which suggests that the mPFC supports short-term memory processes. The putative involvement of the dopaminergic innervation of the mPFC in these mnemonic processes was investigated by evaluating the effects of local infusions of dopaminergic drugs into the mPFC of rats in an operant delayed-matching-to-position (DMTP) task. Trained animals were provided with bilateral guide cannulae aimed at the dorsal part of the mPFC. Two separate groups of rats were tested after microinfusion of several doses of either the dopamine agonist apomorphine (APO) or the dopamine antagonist cis-flupenthixol (FLU). In addition, all animals were tested after infusion of several doses of the muscarinic antagonist scopolamine (SCO). Animals were tested 0 and 135 min after each infusion. At the 0 min interval, neither APO nor FLU affected accuracy of DMTP performance, while both drugs dose-dependently increased response latencies and decreased nosepoke frequencies. At the 135 min interval, APO had almost no effect, whereas the effects of FLU were very prominent. A number of animals no longer responded after infusion of the highest doses of FLU and those that did showed a delay-independent decrease in response accuracy. In contrast, SCO infusions into the mPFC induced a dose- and delay-dependent deterioration of DMTP performance. Taken together, these results support a direct involvement of the rat mPFC in short-term memory processes, although they implicate cholinergic rather than dopaminergic mechanisms in this function.