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Quantification of D 1B (D 5 ) receptors in dopamine D 1A receptor‐deficient mice
Author(s) -
Montague Deidra M.,
Striplin Caryn D.,
Overcash J. Scott,
Drago John,
Lawler Cindy P.,
Mailman Richard B.
Publication year - 2001
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/1098-2396(20010315)39:4<319::aid-syn1015>3.0.co;2-1
Subject(s) - nucleus accumbens , adenylyl cyclase , receptor , dopamine , medicine , dopamine receptor d1 , striatum , endocrinology , dopamine receptor d2 , chemistry , dopamine receptor , wild type , biology , mutant , biochemistry , gene
The unavailability of selective D 1A (D 1 ) or D 1B (D 5 ) dopamine receptor ligands has prevented the direct localization of binding sites for these receptors. Thus, receptor autoradiography with long exposure times was used to detect minor D 1 ‐like binding sites in the brains of D 1A null mutants. Coronal brain sections were prepared from the caudal portion of the prefrontal cortex of homozygous or heterozygous D 1A knockout mice or wildtype mice, and labeled with the D 1 receptor antagonist [ 3 H]‐SCH23390. Slides were dried, and apposed to film with polymer‐calibrated standards for 90 days to allow visualization of any low abundance binding sites. No binding was detected in most regions of homozygote (−/−) mouse brains that have high densities of D 1 binding in wildtype mice (e.g., the striatum, nucleus accumbens, olfactory tubercles or amygdala). Conversely, small, but detectable amounts of D 1 ‐binding were measured in the hippocampus, albeit with a density less than the lowest standard (ca. 20 fmol/mg). Saturation binding of [ 3 H]‐SCH23390 in hippocampal homogenates from homozygous mice confirmed a B max of 12.3 fmol/mg protein with a K D of 0.57 nM. The current work demonstrates directly the presence of D 1B (D 5 ) receptors in hippocampus, and also shows that the loss of functional D 1A gene products almost completely eliminates detectable D 1 ‐binding sites in striatum, as well as in some regions (e.g., the amygdala) where a non‐adenylyl cyclase coupled D 1 receptor has been reported. This indicates that these non‐adenylyl cyclase coupled D 1 ‐like receptors represent alternate signaling pathways rather than novel gene products(s). Synapse 39:319–322, 2001. © 2001 Wiley‐Liss, Inc.