Differential time-course decreases in nonselective, mu-, delta-, and kappa-opioid receptors after focal cerebral ischemia in mice

Background and Purpose-Neuroprotection studies have demonstrated the involv ement of opioids in ischemia, and we have previously demonstrated alteratio ns in B-max of opioidergic receptors after 2 post-MCAO time points in mice. Methods-In the present Study, we have investigated in a detailed manner the postischemic time course of variations in [H-3]diprenorphine (nonselective ), [H-3]DAMGO (mu), [H-3]DADLE (delta), and [H-3]U69593 (kappa) relative bi nding densities after focal cerebral ischemia (0 to 48 hours) in mice. Results-In frontoparietal cortices, our results demonstrate decreases in (1 ) delta receptor densities at 1 to 3 hours after MCAO, (2) mu and nonselect ive binding sites at 6 to 12 hours after MCAO, add (3) kappa receptor densi ties between 6 and 24 hours after MCAO. In the rostral part of the infarct border zone, a decrease in delta-receptors was found concomitant with the e xtension of the infarct core; conversely, the decrease in delta-receptors a ppeared before (6 to 12 hours) macroscopic histological damage, which occur red between 12 hours and 24 hours after MCAO in the caudal part of this are a. In this frontier, mu- and especially kappa-binding sites were decreased later (12 to 48 hours after MCAO). Conclusions-These differential alterations in opioidergic receptors could b e due to the selective sublocalization of receptors, postsynaptically on co rtical interneurons for mu- and delta-receptors versus presynaptically on c ortical afferent pathways for the kappa subtype. Further, our results sugge st that delta- and mu-opioidergic receptors could be markers of infarct ext ension and neuronal death; the study of [H-3]diprenorphine and selective bi nding sites argues in favor of the use of receptor-specific ligands. Finall y, the relative preservation of kappa-receptors might be correlated with th e neuroprotective role of kappa-agonists, as previously reported.