Intrategmental infusion of cocaine decreases dopamine release and enhances norepinephrine release in the medial prefrontal cortex.

We evaluated the effects of local cocaine infusion into the A10 (ventral tegmental area), the cell body of the mesocorticolimbic dopaminergic pathway, on the extracellular concentrations of dopamine and norepinephrine in the medial prefrontal cortex, one of its terminal fields. A 1-ml Hamilton syringe was used to infuse a cocaine solution, either 20 or 200 microM, into the ventral tegmental area of anesthetized rats for 120 min through a microdialysis probe. The pure artificial cerebrospinal fluid (0 microM cocaine) infusion served as a control and a lidocaine (100 microM) infusion was administered to prevent the local anesthetic effect of cocaine. After intrategmental cocaine infusion (either 20 or 200 microM), extracellular dopamine and norepinephrine in the ventral tegmental area both increased significantly to a steady state level (208 +/- 42 and 148 +/- 23% for low dose and 220 +/- 24 and 150 +/- 15% for high dose). Simultaneously, the 200-microM cocaine infusion caused a significant decrease in extracellular dopamine (77 +/- 5%) but an increase in norepinephrine (140 +/- 6%) in the medial prefrontal cortex. The local anesthetic, lidocaine, produced no effects on the dopamine or norepinephrine output (neither in the ventral tegmental area nor in the medial prefrontal cortex). This study not only supports recent findings of an increase in extracellular dopamine and norepinephrine in the ventral tegmental area on intrategmental cocaine infusion, but also demonstrates that cocaine infused locally in the ventral tegmental area can decrease dopamine and increase norepinephrine at a remote terminal area (medial prefrontal cortex). Finally, the introduction rate of cocaine into the ventral tegmental area by retrograde microdialysis was found to be 0.83 ng/min for the low dose and 8.14 ng/min for the high dose.