D2-like dopamine receptors mediate the response to amphetamine in a mouse model of ADHD.
The mechanisms underlying the effects of psychostimulants in attention deficit hyperactivity disorder (ADHD) are not well understood, but indirect evidence implicates D2 dopamine receptors. Here we dissect the components of dopaminergic neurotransmission in the hyperactive mouse mutant coloboma to identify pre- and postsynaptic elements essential for the effects of amphetamine in these mice. Amphetamine treatment reduced locomotor activity in coloboma mice, but induced a robust increase in dopamine overflow suggesting that abnormal regulation of dopamine efflux does not account for the behavioral effect. However, the D2-like dopamine receptor antagonists haloperidol and raclopride, but not the D1-like dopamine receptor antagonist SCH23390, blocked the amphetamine-induced reduction in locomotor activity in coloboma mice, providing direct evidence that D2-like dopamine receptors mediate the effect of amphetamine in these mice. With the precedent established that it is possible to directly antagonize this response, this strategy should prove useful for identifying novel therapeutics in ADHD.
Fan
Xueliang
X
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Hess
Ellen J
EJ
D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D002375:Catalepsy / Q000139:chemically induced / Q000523:psychology; D003103:Coloboma / Q000235:genetics; D004298:Dopamine / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D051379:Mice; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000145:classification / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D009626:Terminology as Topic
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D017448:Receptors, Dopamine D2; D000661:Amphetamine; D000262:Adenylyl Cyclases; D004298:Dopamine