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 (GABAA) 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 GABAA 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 GABAA 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. © 2003 Elsevier Science B.V. All rights reserved.