Blockade of substantia nigra dopamine D1 receptors reduces intravenous cocaine reward in rats

Rationale. We have recently found that blockade of dopamine D1-type receptors in the ventral tegmental area reduces the rewarding effects of intravenous cocaine; here, we explored the possibility that blockade of D1 receptors in the adjacent substantia nigra (SN)-not usually considered part of reward circuitry-might have similar effects. Objective. To test the hypothesis that blockade of dopamine D1 receptors in the SN reduces the rewarding effects of cocaine. Methods. Twenty one rats were prepared with intravenous catheters and with bilateral guide cannulae implanted such that injections could be made directly into the SN or just dorsal to the SN. The rats were trained to self-administer intravenous cocaine (1.0 mg/kg per injection) on a fixed-ratio 1 (FR1) schedule of reinforcement. After stable responding developed, 13 of the animals were tested following pretreatment with bilateral microinjections of SCH 23390 at doses of 0, 1, 2 or 4 mug/0.5 mul into the SN and 8 were tested with injections of 0 mug or 4 mug/0.5 mul into a site 2 mm dorsal to the SN site. Results. Microinjections of SCH 23390 in the SN significantly increased rates of cocaine self-administration, while injections dorsal to SN had no significant effect on responding. Conclusions. These data suggest that blockade of dendritically released DA in the SN reduces the rewarding effects of cocaine. These findings complement accumulating evidence that the rewarding effects of cocaine are not restricted to the drug's ability to elevate dopamine levels in the nucleus accumbens.