CHANGES IN DOPAMINE-DEPENDENT ELECTROCHEMICAL SIGNAL IN THE NUCLEUS-ACCUMBENS ASSOCIATED WITH REPEATED COCAINE INJECTIONS IN RATS

High-speed chronoamperometry with Nafion-coated monoamine-sensitive electrodes was used to evaluate changes in the extracellular dopamine (DA) concentrations in the nucleus accumbens following each of a series of daily cocaine injections (15 mg/kg, i.p.; 5 days and challenge 3-4 days later) in freely moving rats. The first drug injection caused triphasic changes in the DA-dependent electrochemical signal. An initial transitory decrease in signal (equivalent of - 45 nM DA) was followed by a slow increase (from 16 to 100 min; +155 nM) then a subsequent long-term and profound decrease (2-4 h; -100 to 200 nM). Subsequent daily injections did not cause an initial decrease; immediately after cocaine injection the signal increased rapidly to reach a peak of similar to 150-200 nM. The initial component of this signal increase (2-6 min) was more powerful with repeated daily injections, while the amplitude and duration of the signal increase were similar. Similar changes in locomotion were seen following repeated cocaine injections: movement activation occurred with shorter latency and reached a peak earlier, but total amount of counts was relatively stable. The gradual enhancement of the initial components of the electrochemical signal increase following repeated drug injections suggests that the mechanisms of conditioning contribute to the changes of mesolimbic DA accompanying development of cocaine sensitization.