Dopamine receptor density, sensitivity and mRNA 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.