Behavioral responses to cocaine and amphetamine administration in mice lacking the dopamine D1 receptor

Cocaine and amphetamine can induce both short-term and long-term behavioral changes in rodents. The major target for these psychostimulants is thought to be the brain dopamine system. To determine whether the dopamine D1 rece ptor plays a crucial role in the behavioral effects of psychostimulants, we tested both the locomotor and stereotyped behaviors in D1 receptor mutant and wild-type control mice after cocaine and amphetamine treatments. We fou nd that the overall locomotor responses of D1 receptor mutant mice to repea ted cocaine administration were significantly reduced compared to those of the wild-type mice and the responses of the Dr receptor mutant mice to coca ine injections were never significantly higher than their responses to sali ne injections. D1 receptor mutant mice were less sensitive than the wild-ty pe mice to acute amphetamine stimulation over a dose range even though they exhibited apparently similar behavioral responses as those of the wild-typ e mice after repeated amphetamine administration at the 5 mg/kg dose. Immun ostaining experiments indicated that there was no detectable neurotoxicity in the nucleus accumbens in both D1 receptor mutant and wild-type mice afte r repented amphetamine administration. The data suggest that the D1 recepto r plays an essential role in mediating cocaine-induced behavioral changes i n mice. Moreover, the D1 receptor also participates in behavioral responses induced by amphetamine administration. (C) 2000 Published by Elsevier Scie nce B.V. All rights reserved.