ICI 174,864, a selective delta opioid antagonist, reverses the learning impairment produced by [leu]enkephalin.

The role of opioid delta receptors in the learning impairment produced by [leu]enkephalin (LE) in one-way active avoidance conditioning was investigated in mice. LE (30 and 100 micrograms/kg) impaired acquisition of the avoidance response, whereas ICI 174,864 (3.0 mg/kg), a selective delta opioid receptor antagonist, enhanced acquisition. The impairment produced by 100 micrograms/kg LE was completely reversed by 1.0 mg/kg ICI 174,864, a dose of the antagonist that by itself had no effect. Control studies provided evidence that the effects of ICI 174,864 and LE on conditioning cannot be explained by performance variables such as alterations in activity levels or footshock sensitivity. The results suggest that opioid delta receptors play an important role in the modulation of learning, and that the effects of LE on avoidance conditioning are mediated by delta receptors.