Using in vivo extracellular single-cell recording and microiontophoresis, we compared the responsiveness of medial prefrontal cortex (mPFC) neurons (layers V-VI) to dopamine and glutamate in rats that had received repeated amphetamine or saline injections. Neurons from amphetamine-pretreated rats showed increased responsiveness to glutamate and decreased responsiveness to dopamine after three days of withdrawal, suggesting that the mPFC is transiently hyperexcitable during amphetamine withdrawal. Published 2000 Wiley-Liss, Inc.