Cocaine is spontaneously and experimentally self-administered and, when given repeatedly, it induces a stable form of sensitization to a previously assessed minimum active dose. In the present study, triads of rats chronically implanted with a jugular catheter were treated as follows: one animal was trained to self-inject cocaine, while the other two passively received either cocaine or saline whenever the self-administering rat completed the response requirement. After 30 days of stable responding, the animals were sacrificed and dopamine D1 receptor density and adenylyl cyclase activity were measured in different brain areas. Animals receiving cocaine (both self-administering and yoked) showed a down-regulation of dopamine D1 receptor number and of dopamine stimulated adenylyl cyclase activity in the nucleus accumbens, as compared to saline rats. In the olfactory tubercle, dopamine stimulated adenylyl cyclase activity appeared selectively and significantly down-regulated in self-administering animals.