DOPAMINE-RECEPTOR DENSITY, SENSITIVITY AND MESSENGER-RNA LEVELS ARE ALTERED FOLLOWING SELF-ADMINISTRATION OF COCAINE IN THE RAT

The effects of cocaine administration and withdrawal on D-1 and D-2 dopamine receptor number, affinity, and mRNA levels were examined in rats trained to self-administer cocaine for four weeks on a continuous reinforcement schedule. Two hours after the last infusion of cocaine there was a decrease in the number and agonist sensitivity of dopamine D-1 receptors in the anterior forebrain as well as in the limbic region. In contrast, there were no discernible changes in dopamine D-2 receptors in any of the brain regions examined. Examination of dopamine receptor gene expression using Northern blot analysis revealed that there was an increase in D-1 receptor mRNA levels in the forebrain, whereas D-1 and D-2 receptor mRNA levels both were increased in the limbic region. One week following the last infusion of cocaine, D-1 and D-2 receptor mRNA levels had returned to baseline. In the limbic region, D-1 receptor numbers also had normalized by this time, whereas in the forebrain, changes in D-1 receptors persisted. These data indicate that repeated exposure to cocaine induces regional changes in D-1 receptor sensitivity and gene expression, suggesting that the D-1 dopamine system plays an important role in mediating the reinforcing effects of cocaine.