Quantitative autoradiographic mapping of opioid receptors in the brain of δ-opioid receptor gene knockout mice

Content Provider	Semantic Scholar
Author	Goody, Robin J. Oakley, Sarah M. Filliol, Dominique Kieffer, Brigitte Lina Kitchen, I.
Copyright Year	2002
Abstract	Using quantitative receptor autoradiography we have determined if deletion of the delta-opioid receptor gene (Oprd1) results in compensatory changes in the expression of other opioid receptors. Gene targeting was used to delete exon 1 of the mouse delta-opioid receptor gene and autoradiography was carried out on brains from wild-type, heterozygous and homozygous knockout mice. Delta-opioid receptors were labeled with [(3)H]deltorphin I (7 nM), mu- with [(3)H]DAMGO (4 nM), and kappa- with [(3)H]CI-977 (2.5 nM) or [(3)H]bremazocine (2 nM in the presence of DPDPE and DAMGO) and non-specific binding determined with naloxone. [(3)H]Deltorphin I binding was reduced by approximately 50% in heterozygous animals. In homozygous animals specific binding could only be detected after long-term film exposure (12 weeks). Regions exhibiting this residual [(3)H]deltorphin I binding correlated significantly with those demonstrating high levels of the mu-receptor and were abolished in the presence of the mu-agonist DAMGO. Autoradiographic mapping showed significant overall reductions in [(3)H]DAMGO and [(3)H]CI-977 binding throughout the brain following loss of both copies of the Oprd1 gene. In contrast, overall levels of [(3)H]bremazocine binding were higher in brains from -/- than +/+ mice. Our findings suggest that residual [(3)H]deltorphin I binding in the brain of delta-receptor gene knockout mice is the result of cross-reactivity with mu-sites and that there are no delta-receptor subtypes derived from a different gene. Changes in mu- and kappa-receptor labeling suggest compensatory changes in these subtypes in response to the absence of the delta-receptor. The differences in [(3)H]CI-977 and [(3)H]bremazocine binding indicate these ligands show differential recognition of the kappa-receptor.
Starting Page	9
Ending Page	19
Page Count	11
File Format	PDF HTM / HTML
DOI	10.1016/S0006-8993(02)02452-6
PubMed reference number	12113946
Journal	Medline
Volume Number	945
Alternate Webpage(s)	https://api.elsevier.com/content/article/pii/S0006899302024526
Alternate Webpage(s)	https://www.sciencedirect.com/science/article/pii/S0006899302024526?dgcid=api_sd_search-api-endpoint
Alternate Webpage(s)	https://doi.org/10.1016/S0006-8993%2802%2902452-6
Journal	Brain Research
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article