BEHAVIORAL ACID NEUROCHEMICAL SENSITIZATION FOLLOWING COCAINE SELF-ADMINISTRATION

To determine if behavioral and neurochemical sensitization results fro m cocaine self-administration, rats were trained to self-administer co caine for 20 consecutive days(26.5 +/- 2.6 mg/kg, IV/day). At 24 h or 21 days after discontinuing cocaine self-administration or yoked salin e control, rats were administered an acute injection of saline IP, fol lowed 60 min later by cocaine (15 mg/kg, IF). Cocaine-induced changes in motor activity were monitored with a photocell apparatus and altera tions in extracellular dopamine in the ventral striatum were measured with microdialysis. There was no difference between treatment groups i n the basal level of extracellular dopamine as determined by in vitro calibration. Neither the motor stimulant response nor the increase in extracellular dopamine following an acute cocaine challenge given afte r 24 h of withdrawal was different between rats which self-administere d cocaine and yoked saline controls. However, when the cocaine challen ge was given 21 days after discontinuing cocaine self-administration b oth the motor response and extracellular dopamine content in the ventr al striatum were significantly augmented in rats that self-administere d cocaine. While no correlation was observed between the average amoun t of cocaine self-administered each day and the cocaine-induced altera tions in extracellular dopamine at either 24 h or 21 days of withdrawa l, a significant positive correlation was measured between the increas e in photocell counts and the average daily cocaine administration at 21 days of withdrawal. These data show that cocaine self-administratio n produces an augmentation in the acute behavioral and neurochemical r esponse to a cocaine challenge that resembles the sensitization previo usly demonstrated with repeated noncontingent administration.