Toward a molecular understanding of psychostimulant actions using genetically engineered dopamine receptor knockout mice as model systems.
A major focus in studying the progression and prevention of addictive diseases has been to understand the molecular and cellular mechanisms underlying drug addiction. The brain dopaminergic system plays a central role in reward and motivation and is thought to be the main neural substrate for the actions of abusive drugs. We have used the gene targeting technology to generate dopamine D1 and D3 receptor knockout mice and used these mice as model systems to gain a molecular understanding of acute effects of psychostimulants cocaine and amphetamine. The use of a combined approach involving behavioral, electrophysiological as well as molecular studies has allowed us to define initially the roles of dopamine D1 and D3 receptors in the acute effects of psychostimulants and will enable us to understand mechanisms underlying their chronic actions in the future.
Zhang
J
J
Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati College of Medicine, OH 45267-0521, USA.
Xu
M
M
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics*; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics*; D023421:Models, Animal; D008959:Models, Neurological; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D050637:Receptors, Dopamine D3
D000697:Central Nervous System Stimulants; C493594:Drd3 protein, mouse; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D000661:Amphetamine; D003042:Cocaine