Studies in vivo with ICI 174864 and [D-Pen2, D-Pen5]enkephalin

We studied the in vivo pharmacology of a selective agonist (DPDPE) and a selective antagonist (ICI 174864) at delta opioid receptors. ICI 174864 (10 micrograms icv) caused postural abnormalities, barrel rotation and hypothermia in rats. DPDPE induced behavioural arousal (at 75 micrograms icv) and barrel rotation (at 125 micrograms) in rats. ICI 174864 (10 micrograms icv) attenuated acetic acid induced writhing in mice. This action was antagonized by naloxone (10 but not 2 mg/kg s.c.). A lower, non-agonist dose of ICI 174864 (5 micrograms) antagonized DPDPE (3 micrograms icv) in this test without affecting DAGO (0.0006 micrograms icv), a selective agonist at mu receptors. In the mouse tail flick test, ICI 174864 (10-50 micrograms icv) did not significantly antagonize the agonist actions of DPDPE (40 micrograms icv) or DAGO (0.3 micrograms icv). At 10-50 micrograms icv, ICI 174864 had no marked effect on gastrointestinal transit in mice. ICI 174864 (25 micrograms icv or 20 mg/kg s.c.) did not interact with mu opioid receptors in mice rendered physically dependent on morphine.