Changes in extracellular dopamine during cocaine self-administration in squirrel monkeys

Environmental cues are thought to play a role in drug craving, leading to the high relapse rate observed in cocaine abusers. Cocaine-paired cues can reinstate cocaine-maintained behavior in rodents and nonhuman primates and can induce changes in dopamine levels in the rodent striatum. In the present study, squirrel monkeys were trained to self-administer cocaine under a second-order schedule, and then were implanted with guide cannulae targeted at the caudate nucleus. Caudate dopamine levels were measured while the animals performed the behavioral task, self-administering cocaine or saline under extinction conditions. In addition, animals received noncontingent (passive) cocaine infusions yoked to the drug self-administration sessions. Cocaine administration increased dopamine levels 2-fold, but a leftward shift was seen in the peak effect in animals self-administering cocaine as compared to animals passively receiving cocaine. Moreover, dopamine levels began to decline during the experimental session when animals were self-administering cocaine, even though they continued to receive cocaine injections. In contrast, dopamine levels declined below baseline during the session when animals were given access to saline. The results suggest that the environmental context associated with drug self-administration can modulate cocaine-induced elevations in extracellular dopamine. Synapse 56:129-134, 2005. (c) 2005 Wiley-Liss, Inc.