Neurochemical changes in dopamine D1, D3 and D1/D3 receptor knockout mice.
Neurochemical changes were examined in dopamine D1 receptor knockout (D1(-/-)), dopamine D3 receptor knockout (D3(-/-)) and dopamine D1/D3 receptor double knockout (D1(-/-)D3(-/-)) mice. The level of dopamine D1- and D2-like receptors and gamma-aminobutyric acid (GABA(A)) receptor was assessed by ligand autoradiography and dopamine D1- and D2 receptor, enkephalin, dynorphin and substance P transcripts measured by in situ hybridization. D1(-/-) mice had normal GABA(A) receptor levels, reduced dynorphin and substance P, and increased enkephalin mRNA and dopamine D2-like binding. D1(-/-)D3(-/-) mice evidenced decreased dynorphin and substance P but normal enkephalin expression, whereas dopamine D2-like and GABA(A) receptor binding were increased. Major changes occur in substance P and dynorphin expression in D1(-/-) mice and these changes are unaffected by loss of dopamine D3 receptors. Upregulated dopamine D2-like binding and enkephalin in D1(-/-) mice may be due to decreased dopamine turnover. Upregulated enkephalin in D1(-/-) mice is dependent on functional dopamine D3 receptors.
Wong
John Y F
JY
Neurosciences Group, Monash University, Department of Medicine, Monash Medical Centre, Level 5 Block E, 246 Clayton Road, Clayton, Victoria 3168, Australia.
Clifford
Jeremiah J
JJ
Massalas
Jim S
JS
Finkelstein
David I
DI
Horne
Malcolm K
MK
Waddington
John L
JL
Drago
John
J
D000818:Animals; D001345:Autoradiography; D050483:Dopamine Plasma Membrane Transport Proteins; D004399:Dynorphins / Q000096:biosynthesis / Q000378:metabolism; D004745:Enkephalins / Q000096:biosynthesis / Q000378:metabolism; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D011485:Protein Binding; D012333:RNA, Messenger / Q000096:biosynthesis; D017447:Receptors, Dopamine D1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D011963:Receptors, GABA-A / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D013687:Telencephalon / Q000378:metabolism*
D050483:Dopamine Plasma Membrane Transport Proteins; C493594:Drd3 protein, mouse; D004745:Enkephalins; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D013373:Substance P; D004399:Dynorphins