Mu and delta opioid receptor analgesia, binding density, and mRNA levels in mice selectively bred for high and low analgesia

The present study examined mu and delta opioid analgesia, receptor binding, and receptor mRNA levels in lines of mice from two selective breeding proj ects of relevance to opioid analgesia. Large differences were observed in t he analgesic potency of [D-Ala(2), NMPhe(4), Gly-ol]enkephalin (DAMGO), [D- Pen(2,5)]enkephalin (DPDPE), and [D-Ala(2)]deltorphin II (DELT), selective mu, delta,, and delta, opioid receptor agonists, respectively, in mice sele ctively bred for high (HA) and low (LA) swim stress-induced analgesia (SIA) . HAR and LAR mice, selectively bred for high and low levorphanol analgesia , respectively, display equally large differences in their analgesic sensit ivity to DAMGO, modest differences in sensitivity to DPDPE, and no differen ces in sensitivity to DELT. These sizable genotypic differences in analgesi c potency were accompanied by HA/LA and HAR/LAR differences in whole-brain homogenate [H-3]DPDPE and/or [H-3]DELT, but paradoxically not [H-3]DAMGO, b inding. Solution hybridization of mRNA extracts encoding mu (MOR-1) or delt a (DOR-1) opioid receptors indicated some regional differences in gene expr ession between high and low lines. Surprisingly, differences in these in vi tro markers were often in the direction of LAR > HAR. The present data indi cate that selection for either SSIA or levorphanol analgesia produces diffe rential effects on mu and delta opioid analgesia that are accompanied by al terations on in vitro assays, the significance of which remains to be deter mined. The data are discussed with regard to the utility of in vitro biolog ical markers and genetic models of analgesia. (C) 1999 Elsevier Science B.V . All rights reserved.