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 D1 and D2 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 D1 receptors in the anterior forebrain as well as in the limbic region. In contrast, there were no discernible changes in dopamine D2 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 D1 receptor mRNA levels in the forebrain, whereas D1 and D2 receptor mRNA levels both were increased in the limbic region. One week following the last infusion of cocaine, D1 and D2 receptor mRNA levels had returned to baseline. In the limbic region, D1 receptor numbers also had normalized by this time, whereas in the forebrain, changes in D1 receptors persisted. These data indicate that repeated exposure to cocaine induces regional changes in D1 receptor sensitivity and gene expression, suggesting that the D1 dopamine system plays an important role in mediating the reinforcing effects of cocaine.