DIFFERENTIAL EFFECTS OF LEU- AND MET-ENKEPHALIN ON NARCOTIC-INDUCED ENHANCEMENT OF NALOXONE EFFICACY

Summary In superfusion experiments in vitro , facilitation of naloxone-releasable morphine was observed with slices of corpus striatum which were obtained from mice pretreated in vivo with 20 mg/kg leu-enkephalin (LE) i.p. 15 min before sacrifice. Preincubation of striatal slices for 15 min with LE in vitro at concentrations ranging from 1 nM to 0.1 pM also enhanced the morphine-releasing effect of naloxone. Met-enkephal in pretreatment (ME) did not exhibit any of the above effects. Simultaneous incubation of an equimolar concentration of naloxone blocked this enhancing effect of leu-enkephalin. Prior incubation with LE did not influence naltrexone-releasable 3 H-naltrexone but markedly enhanced morphine-releasable 3 H-naltrexone and morphine-or levorphanol-releasable 3 H-morphine. We suggest that the apparent increase in naloxone efficacy is mediated by narcotic agonists and LE potentiates this effect. Similar effects by LE on the narcotic-induced enhancement of naloxone efficacy were observed in vivo .