The dopaminergic pathway from the ventral tegmental area (VTA) to the nucleus accumbens (NAcc) is well known to be involved in the reinforcing properties of many drugs of abuse. The medial prefrontal cortex (mPFC) has been shown to exhibit significant influence over activity in this pathway, and has also been implicated in drug abuse. The present experiment investigated the ability of D1 activity in the mPFC to influence accumbal dopamine levels. NAcc dopamine (DA) was monitored before, immediately after, and 24 h following mPFC infusion of a D1 agonist (SKF 38393), D1 antagonist (SCH 23390), or a vehicle solution. Immediately following infusion of dopaminergic agents or vehicle, no significant changes in accumbal DA were observed. However, 24 h following infusion of the antagonist but not the agonist, significant elevations of accumbal DA were observed. Since elevated NAcc DA was only observed 24 h after treatment, these results provide evidence that long-term neural adaptations can be induced by transient neuropharmacological treatment.