| First Author | Goody RJ | Year | 2002 |
| Journal | Brain Res | Volume | 945 |
| Issue | 1 | Pages | 9-19 |
| PubMed ID | 12113946 | Mgi Jnum | J:78285 |
| Mgi Id | MGI:2183913 | Doi | 10.1016/s0006-8993(02)02452-6 |
| Citation | Goody RJ, et al. (2002) Quantitative autoradiographic mapping of opioid receptors in the brain of delta-opioid receptor gene knockout mice. Brain Res 945(1):9-19 |
| abstractText | 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), micro- 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 micro-receptor and were abolished in the presence of the micro-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 micro-sites and that there are no delta-receptor subtypes derived from a different gene. Changes in micro- 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. |
