ALTERED COCAINE POTENCY IN THE NUCLEUS-ACCUMBENS FOLLOWING 7-DAY WITHDRAWAL FROM INTERMITTENT BUT NOT CONTINUOUS TREATMENT - VOLTAMMETRIC ASSESSMENT OF DOPAMINE UPTAKE IN THE RAT

Using in vitro fast scan cyclic voltammetry, we measured cocaine poten cy for inhibiting dopamine uptake/clearance in accumbens slices 7 days after withdrawal from chronic cocaine pretreatments. Rats were pretre ated with 40 mg/kg per day for 14 days, either via continuous osmotic minipumps or by once-daily injections. The cocaine potency was subsequ ently assessed for endogenous and exogenous dopamine applied via singl e-pulse electrical stimulation and caged-dopamine photolysis, respecti vely. Under baseline conditions, no differences in either endogenous o r exogenous dopamine kinetics were observed in the two cocaine pretrea tment groups. In contrast, the potency of bath-applied cocaine for inh ibiting endogenous dopamine uptake was enhanced in the intermittent in jection group with no change in the continuous infusion group. The sel ective increase in the cocaine potency following injections was also d emonstrable for clearance of photo-applied DA. The enhanced cocaine po tency in the accumbens slices following 7 days of withdrawal is consis tent with the residual sensitization to cocaine-induced locomotion fol lowing daily cocaine injections. Behavioral tolerance following contin uous infusion, on the other hand, may be mediated via a mechanism dist inct from altered dopamine uptake.