Modifications of dopamine D-1 receptor complex in rats self-administering cocaine

Cocaine is spontaneously and experimentally self-administered and, when giv en repeatedly, it induces a stable form of sensitization to a previously as sessed minimum active dose. In the present study, triads of rats chronicall y implanted with a jugular catheter were treated as follows: one animal was trained to self-inject cocaine, while the other two passively received eit her cocaine or saline whenever the self-administering rat completed the res ponse requirement. After 30 days of stable responding, the animals were sac rificed and dopamine D-1 receptor density and adenylyl cyclase activity wer e measured in different brain areas. Animals receiving cocaine (both self-a dministering and yoked) showed a down-regulation of dopamine D-1 receptor n umber and of dopamine stimulated adenylyl cyclase activity in the nucleus a ccumbens, as compared to saline rats. In the olfactory tubercle, dopamine s timulated adenylyl cyclase activity appeared selectively and significantly down-regulated in self-administering animals. (C) 1998 Elsevier Science B.V . All rights reserved.