FLUCTUATIONS IN NUCLEUS-ACCUMBENS DOPAMINE CONCENTRATION DURING INTRAVENOUS COCAINE SELF-ADMINISTRATION IN RATS

Fluctuations in extracellular dopamine and DOPAC levels in nucleus acc umbens septi (NAS) were monitored in 1-min microdialysis samples taken from rats engaged in intravenous cocaine self-administration. For fou r rats the dose per injection was fixed at 2.0 mg/kg; for four others the dose per injection was varied irregularly, from one response to th e next, between three levels (0.5, 1.0 and 2.0 mg/kg). Regardless of t he dosing regimen, extracellular dopamine levels were tonically elevat ed by 200-800% within the cocaine self-administration periods, fluctua ting phasically within this range between responses. In the fixed dose condition, the phasic increases following each injection (and the pha sic decreases preceding them) averaged approximately 50% of the mean t onic elevation. Phasic fluctuations in dopamine levels remained time-l ocked to lever-presses even when response rate was irregular, because of the variable dose condition. In the variable dose condition greater increases in dopamine and longer inter-response times followed inject ions of the higher doses; dopamine fluctuations were consistent with t he multiple-infusion pharmacokinetics of cocaine. DOPAC levels showed a slow tonic depression during cocaine self-administration, but indivi dual injections were not associated with discernible phasic fluctuatio ns of DOPAC. These data are consistent with the hypothesis that fallin g dopamine levels trigger successive responses in the intravenous coca ine self-administration paradigm, but inconsistent with the notion tha t extracellular dopamine levels are depleted at the times within sessi ons when the animal initiates drug-seeking responses.