Reduction of the rewarding effect of brain stimulation by a blockade of dopamine D1 receptor with SCH 23390.

The subtype of dopamine receptor related to the rewarding effect of brain stimulation was determined in 17 rats. The animals were trained to contact a dry spout to receive stimulation through electrodes implanted into the lateral hypothalamic area, ventral tegmental area, or dorsal raphe nucleus. The dopamine D1 blocking agent SCH 23390, 0.08 mg/kg IP, completely suppressed responding. The D2 receptor blocker sulpiride, 50 mg/kg IP, or the serotonin receptor blocker metergoline, 5 mg/kg IP, did not suppress responding. The ED50 for SCH 23390 was 0.022 mg/kg IP. In a runway, rats were trained to run for rewarding goal stimulation consisting of a train of pulses delivered to the lateral hypothalamus. After injection of SCH 23390, 0.01 mg/kg IP, animals showed significantly slower running speed, but their speed returned to normal if the number of pulses in the goal stimulation was increased 2.6 times. These results indicate that blockade of D1 receptors, but not D2 receptors, reduces the rewarding effect of brain stimulation.