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Abstract
In the present autoradiographic study, we took advantage of 5-hydroxytryptamine 7 (5-HT 7) receptor knockout mice to analyze the brain distribution of 5-HT 7 receptor binding sites using [ 3H]5-carboxamidotryptamine (5-CT; a 5-HT 1A/1B/1D/5/7 receptor ligand) and [ 3H]8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT; a 5-HT 1A/7 receptor ligand). Low to moderate densities of [ 3H]5-CT (2 nM) binding sites insensitive to pindolol (10 μM, for 5-HT 1A/1B receptor blockade) and GR-127935 (1 μM; for 5-HT 1D receptor blockade) were observed in wild-type mice (mainly in thalamus and hypothalamus) but not in 5-HT 7 receptor knockout mice. Surprisingly, moderate to high densities of [ 3H]8-OH-DPAT (10 nM) binding sites insensitive to pindolol (10 μM) remained in 5-HT 7 receptor knockout mouse brain. These non-5-HT 1A, non-5-HT 7 binding sites were found to be adrenergic α 2A receptor binding sites. In α 2A receptor knockout mice low to moderate densities of [ 3H]8-OH-DPAT binding sites insensitive to pindolol but sensitive to the selective 5-HT 7 receptor antagonist SB-269970 (300 nM) were observed mainly in thalamus and hypothalamus. Therefore, in addition to 5-HT 1A and 5-HT 7 binding sites, [ 3H]8-OH-DPAT also binds to α 2A receptor binding sites in wild-type mouse brain. [ 3H]8-OH-DPAT (in the presence of pindolol and 1 μM RX-821002 for α 2 receptor blockade) and [ 3H]5-CT (in the presence of pindolol and GR-127935) bind to a similar receptor binding population corresponding to 5-HT 7 binding sites. Detailed anatomical mapping of 5-HT 7 receptor binding sites in wild-type mouse brain was then performed using both radioligands in the presence of suitable pharmacological agents for non-5-HT 7 receptor binding sites blockade. The mapping revealed binding sites consistent with the mRNA distribution with the highest densities found in anterior thalamic nuclei.
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