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 μg icv) caused postural abnormalities, barrel rotation and hypothermia in rats. DPDPE induced behavioural arousal (at 75 μg icv) and barrel rotation (at 125 μg) in rats. ICI 174864 (10 μg 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 μg) antagonized DPDPE (3 μg icv) in this test without affecting DAGO (0.0006 μg icv), a selective agonist at mu receptors. In the mouse tail flick test, ICI 174864 (10-50 μg icv) did not significantly antagonize the agonist actions of DPDPE (40 μg icv) or DAGO (0.3 μg icv). At 10-50 μg icv, ICI 174864 had no marked effect on gastrointestinal transit in mice. ICI 174864 (25 μg icv or 20 mg/kg s.c.) did not interact with mu opioid receptors in mice rendered physically dependent on morphine.