Behavioral and neurochemical sensitization following cocaine self-administration.

To determine if behavioral and neurochemical sensitization results from cocaine self-administration, rats were trained to self-administer cocaine 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 saline control, rats were administered an acute injection of saline IP, followed 60 min later by cocaine (15 mg/kg IP). Cocaine-induced changes in motor activity were monitored with a photocell apparatus and alterations in extracellular dopamine in the ventral striatum were measured with microdialysis. There was no difference between treatment groups in 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 after 24 h of withdrawal was different between rats which self-administered cocaine and yoked saline controls. However, when the cocaine challenge was given 21 days after discontinuing cocaine self-administration both the motor response and extracellular dopamine content in the ventral straitum were significantly augmented in rats that self-administered cocaine. While no correlation was observed between the average amount of cocaine self-administered each day and the cocaine-induced alterations in extracellular dopamine at either 24 h or 21 days of withdrawl, a significant positive correlation was measured between the increase in photocell counts and the average daily cocaine administration at 21 days of withdrawl. These data show that cocaine self-administration produces an augmentation in the acute behavioral and neurochemical response to a cocaine challenge that resembles the sensitization previously demonstrated with repeated noncontingent administration.