Stimulation of δ 1 - and δ 2 -opioid receptors produces amnesia in mice

The effects of intracerebroventricular administration of δ 1 - and δ 2 -selective opioid receptor agonists on spontaneous alternation performance, elevated plus-maze behavior and passive avoidance learning including step-down and step-through types were examined in mice. Although the δ 1 -selective opioid receptor agonist, [ d -Pen2, l -Pen5]enkephalin (DPLPE) (1–10 μ g) or the δ 2 -selective opioid receptor agonist, [ d -Ala 2 ]deltorphin II (deltorphin) (1–10 μ g) did not markedly affect spontaneous alternation performance or elevated plus-maze behavior, DPLPE (1, 3 and/or 10 μ g) and deltorphin (3 and 10 μ g) inhibited passive avoidance learning including step-down and step-through types. The δ 1 -selective opioid receptor antagonist, 7-benzylidenenaltrexone (3.5 ng), and the δ 2 -selective opioid receptor antagonist, naltriben (19 ng), significantly antagonized the inhibitory effects of DPLPE (3 μ g) and deltorphin (3 μ g) on passive avoidance learning, respectively. In contrast, DPLPE (3 μ g) or deltorphin (3 μ g) did not markedly influence behavioral responses induced by electroshocks during training of passive avoidance learning. Moreover, DPLPE (0.3–3 μ g) or deltorphin (0.3–3 μ g) failed to significantly affect the radiant heat-induced nociceptive responses. These results suggest that stimulation of δ 1 - and δ 2 -opioid receptors produces amnesia, depending on the learning tasks used.