DRUG-ASSOCIATED AND BEHAVIOR-ASSOCIATED CHANGES IN DOPAMINE-RELATED ELECTROCHEMICAL SIGNALS DURING INTRAVENOUS HEROIN SELF-ADMINISTRATION IN RATS

High-speed chronoamperometry was used to monitor dopamine-related elec trochemical signals in the nucleus accumbens of rats allowed to self-a dminister heroin intravenously and rats that received similar injectio ns passively. Rats self-administered 100 mug/kg of heroin at approxima tely 20-min intervals. Dopamine-related electrochemical signals increa sed monotonically after the first injection of each day; the effect wa s weaker on the first than on the second and subsequent days. The seco nd and subsequent injections in each session caused biphasic effects: the initial effect was a decrease in signal-a minor one when compared to the increase caused by the first injection-and this was followed by an increase that brought the signal back to or somewhat higher than t he level at the time of the injection. Over the course of each 4-h ses sion, the electrochemical signal reached and fluctuated around an elev ated plateau; doubling the injection dose did not elevate this plateau but did cause larger phasic decreases and subsequent increases. Quali tatively similar electrochemical changes were seen in the animals pass ively receiving the drug, but there were two notable quantitative diff erences. First, in the passive animals the initial depressions in sign al were of shorter duration. Second, in the passive animals (which wer e injected at intervals determined by the self-administering animals) the electrochemical signal reached a maximum and began to fall prior t o the time of the next injection; in the animals that self-administere d the drug, the signal was still rising at the time of the next inject ion. The changes in electrochemical signal are unlikely to represent f luctuations of ascorbate or dopamine metabolites; thus it appears that whereas self-administered heroin injections cause a slow and long-las ting elevation of extracellular dopamine concentration, short-term inc reases in dopamine concentration are associated with the behavioral ac tivation that precedes the injections and it is short-term decreases t hat appear to be associated with the period usually thought to be most significant for positive reinforcement.