Binding in vivo of selective μ and δ opioid agonists: Localization by autoradiography

The in vivo binding properties of cerebral opioid receptors were investigated in mice after intracerebroventricular (i.c.v.) injections of iodinated FK33-824 and [D.Ala 2]deltorphil-I which behave in vitro as highly selective ligands possessing high affinity for μ and δ receptors, respectively. [ 125I]FK33-824 and [ 125I][D.Ala 2] deltorphin-I exhibited similar diffusion kinetics after i.c.v. injection and bound specifically to sites characterized pharmacologically as μ and δ receptors respectively. Autoradiographic analysis revealed that after i.c.v. administration, concentrations of [ 125I]FK33-824 and [ 125I][D.Ala 2]deltorphin-I remained higher in the circumventricular than in the deep structure of the brain and that specific sites labelled in vivo were differently distributed from those observed after in vitro labelling. FK33-824 was 250 times more analgesic than [D.Ala 2]deltorphin-I in the tail-flick test and at doses producing a similar analgesia, [D.Ala 2]deltorphin-I occupied a high proportion of μ receptors. Furthermore, analgesic effect of [D.Ala 2]deltorphin-I was antagonized by pretreatment with naltrexone but not by naltrindole, a selective antagonist of δ-opioid receptors. These experiments reveal the localization of μ and δ opioid receptors reached after i.c.v. injection and provide evidence to support the suggestion that δ-opioid receptors contribute little or none to the supraspinal antinociception.