Pharmacologic neuroimaging of the ontogeny of dopamine receptor function.
Characterization of the ontogeny of the cerebral dopaminergic system is crucial for gaining a greater understanding of normal brain development and its alterations in response to drugs of abuse or conditions such as attention-deficit hyperactivity disorder. Pharmacological MRI (phMRI) was used to determine the response to dopamine transporter (DAT) blockers cocaine and methylphenidate (MPH), the dopamine releaser D-amphetamine (AMPH), the selective D1 agonist dihydrexidine, and the D2/D3 agonist quinpirole in young (<30 days old) and adult (>60 days old) rats. In adult rats, cocaine (0.5 mg/kg i.v.) or MPH (2 mg/kg) induced primarily positive cerebral blood volume (rCBV) changes in the dopaminergic circuitry, but negative rCBV changes in the young animals. Microdialysis measurements in the striatum showed that young rats have a smaller increase in extracellular dopamine in response to cocaine than adults. The young rats showed little rCBV response to the selective D1 agonist dihydrexidine in contrast to robust rCBV increases observed in the adults, whereas there was a similar negative rCBV response in the young and adult rats to the D2 agonist quinpirole. We also performed a meta-analysis of literature data on the development of D1 and D2 receptors and the DAT. These data suggest a predominance of D2-like over D1-like function between 20 and 30 days of age. These combined results suggested that the dopamine D1 receptor is functionally inhibited at young age.
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. iris@nmr.mgh.harvard.edu
Y Iris
YI
Chen
Ji-Kyung
JK
Choi
Haibo
H
Xu
Jiaqian
J
Ren
Susan L
SL
Andersen
Bruce G
BG
Jenkins
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology*; D000661:Amphetamine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003042:Cocaine / Q000378:metabolism / Q000494:pharmacology; D018491:Dopamine Agonists / Q000378:metabolism / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000819:agonists / Q000037:antagonists & inhibitors; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008774:Methylphenidate / Q000378:metabolism / Q000494:pharmacology; D017551:Microdialysis; D010617:Phenanthridines / Q000378:metabolism / Q000494:pharmacology; D019257:Quinpirole / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D017448:Receptors, Dopamine D2 / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D012039:Regional Blood Flow
D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D010617:Phenanthridines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D008774:Methylphenidate; D019257:Quinpirole; C061532:dihydrexidine; D000661:Amphetamine; D003042:Cocaine