Biphasic changes in mesolimbic dopamine signal during cocaine self-administration.

High-speed chronoamperometry with Nafion-coated carbon fiber microelectrodes was used to follow changes in extracellular dopamine (DA) concentration in the nucleus accumbens of rats during intravenous cocaine self-administration (SA) behavior. An abrupt, transient decrease in DA-dependent electrochemical signal was found immediately after cocaine SA, whereas the signal slowly increased preceding each lever-press, reaching a peak at the operant response. Procaine, a local anesthetic, also maintained SA behavior in rats previously trained to SA cocaine. Similar to that seen after cocaine, a dose-dependent, abrupt decrease in electrochemical signal was seen following procaine SA, although the pre-pressing signal increase was absent. These data suggest that short-term inhibition of mesolimbic DA release is an immediate consequence of intravenous cocaine SA and may be correlated with the drug's rewarding action. This release inhibition appears to be independent of cocaine's ability to inhibit DA reuptake, a mechanism that would lead to an accumulation of extracellular DA and an increase in electrochemical signal. The coexistence of these two functionally opposite actions of cocaine on mesolimbic DA neurons may be important in mediating cocaine's unique psychogenic and addictive properties.