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 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.