Neurochemical changes in dopamine D1, D3 and D1/D3 receptor knockout mice

• Published in: European journal of pharmacology Vol. 472; no. 1; pp. 39 - 47
• Main Authors: Wong, John Y.F, Clifford, Jeremiah J, Massalas, Jim S, Finkelstein, David I, Horne, Malcolm K, Waddington, John L, Drago, John
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 04-07-2003; Elsevier
• Subjects: Animals; Autoradiography; Biological and medical sciences; Dopamine Plasma Membrane Transport Proteins; Dopamine receptor; Dynorphin; Dynorphins - biosynthesis; Dynorphins - metabolism; Enkephalin; Enkephalins - biosynthesis; Enkephalins - metabolism; Gene targeting; Ligands; Male; Medical sciences; Membrane Glycoproteins; Membrane Transport Proteins - metabolism; Mice; Mice, Knockout; Nerve Tissue Proteins; Protein Binding; Receptors, Dopamine D1 - biosynthesis; Receptors, Dopamine D1 - genetics; Receptors, Dopamine D1 - metabolism; Receptors, Dopamine D2 - biosynthesis; Receptors, Dopamine D2 - genetics; Receptors, Dopamine D2 - metabolism; Receptors, Dopamine D3; Receptors, GABA-A - metabolism; Receptors, Muscarinic - metabolism; RNA, Messenger - biosynthesis; Substance P; Substance P - metabolism; Telencephalon - metabolism; Gene targeting; Dopamine receptor; Substance P; Dynorphin; Enkephalin
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(03)01862-4

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 γ-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.