Effects of repeated injections of cocaine on D1 and D2 dopamine receptors in rat brain.

In order to determine if chronic administration of cocaine produced long-lasting alterations in dopamine receptor binding, rats were treated with single daily injections of cocaine (0, 10, or 20 mg/kg) for 15 consecutive days and killed either 20 min or 2 weeks after the last injection. The density of D1 binding sites in frontal cortex was either unchanged (10 mg/kg) or slightly increased (20 mg/kg) 20 min after the last daily injection, but was decreased 2 weeks later. D1 sites in striatum were decreased both immediately and 2 weeks after the injection regimen. Decreases in D1 binding site density in nucleus accumbens were observed only immediately after the last injection. In contrast to these effects on D1 binding sites, D2 binding sites were decreased in striatum and frontal cortex and increased in the nucleus accumbens 20 min after repeated cocaine, but were unaffected 2 weeks after repeated cocaine. Computer-assisted analysis of the saturation isotherms revealed that chronic administration of cocaine did not affect the affinity (Kd) of the radioligands used to label D1 or D2 sites. These findings suggest that repeated administration of cocaine results in long-term decreases in D1 binding sites in striatum and frontal cortex and transient decreases in D2 binding sites. Furthermore, cocaine caused opposite, transient effects on D1 and D2 site density in nucleus accumbens.