Cellular responses to psychomotor stimulant and neuroleptic drugs are abnormal in mice lacking the D1 dopamine receptor.
Stimulation of dopamine D1 receptors has profound effects on addictive behavior, movement control, and working memory. Many of these functions depend on dopaminergic systems in the striatum and D1-D2 dopamine receptor synergies have been implicated as well. We show here that deletion of the D1 dopamine receptor produces a neural phenotype in which amphetamine and cocaine, two addictive psychomotor stimulants, can no longer stimulate neurons in the striatum to express cFos or JunB or to regulate dynorphin. By contrast, haloperidol, a typical neuroleptic that acts preferentially at D2-class receptors, remains effective in inducing catalepsy and striatal Fos/Jun expression in the D1 mutants, and these behavioral and neural effects can be blocked by D2 dopamine receptor agonists. These findings demonstrate that D2 dopamine receptors can function without the enabling role of D1 receptors but that D1 dopamine receptors are essential for the control of gene expression and motor behavior by psychomotor stimulants.
Moratalla
R
R
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology 02139, USA.
Xu
M
M
Tonegawa
S
S
Graybiel
A M
AM
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D017353:Gene Deletion; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000235:genetics*
D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D017447:Receptors, Dopamine D1; D000661:Amphetamine; D003042:Cocaine; D006220:Haloperidol