Phasic inhibition of dopamine uptake in nucleus accumbens induced by intravenous cocaine in freely behaving rats

A new approach combining fast-scan cyclic voltammetry with iontophoretic do pamine delivery was used in freely behaving rats to evaluate the time-cours e of dopamine uptake inhibition in nucleus accumbens induced by intravenous cocaine at a dose (1.0 mg/kg) known to maintain self-administration behavi or. Cocaine significantly increased the decay time of the dopamine response without altering its magnitude or time to peak. An increase in decay time was evident at 2 min, peaked at 6 min (+ 87%), and decreased to baseline at 18 min after a single cocaine injection. The change in decay time was simi lar in all rats and remained essentially the same, albeit slightly larger, for subsequent cocaine injections both within a session and over repeated s essions. The change in dopamine decay time did not correlate with cocaine-i nduced motor activation, which was maximal during the first minute after in jection and decreased slowly over the next 20 min. Our data provide direct evidence for a phasic change in dopamine uptake ind uced by intravenous cocaine under behaviorally relevant conditions. The rel atively slow and gradual development of dopamine uptake inhibition, which p eaks at times when behaving rats self-inject cocaine, is inconsistent with the suggested role of this mechanism in the acute rewarding (euphoric) effe cts of self-injected cocaine, but supports its role in the activational and motivational aspects of drug-seeking and drug-taking behavior. Because int ravenous cocaine enters the brain rapidly and peaks in neural tissue (1-2 m in) long before it effectively inhibits dopamine uptake (6 min), it appears that some of the acute psychoemotional ("rush"), behavioral, autonomic, an d neuronal effects of this drug, which are apparently resistant to dopamine receptor blockade, are mediated via rapid central or peripheral mechanisms independent of monoamine uptake. Published by Elsevier Science Ltd.