Stimulation of delta1- and delta2-opioid receptors produces amnesia in mice.

The effects of intracerebroventricular administration of delta1- and delta2-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 delta1-selective opioid receptor agonist, [D-Pen2,L-Pen5]enkephalin (DPLPE) (1-10 microg) or the delta2-selective opioid receptor agonist, [D-Ala2]deltorphin II (deltorphin) (1-10 microg) did not markedly affect spontaneous alternation performance or elevated plus-maze behavior, DPLPE (1, 3 and/or 10 microg) and deltorphin (3 and 10 microg) inhibited passive avoidance learning including step-down and step-through types. The delta1-selective opioid receptor antagonist, 7-benzylidenenaltrexone (3.5 ng), and the delta2-selective opioid receptor antagonist, naltriben (19 ng), significantly antagonized the inhibitory effects of DPLPE (3 microg) and deltorphin (3 microg) on passive avoidance learning, respectively. In contrast, DPLPE (3 microg) or deltorphin (3 microg) did not markedly influence behavioral responses induced by electroshocks during training of passive avoidance learning. Moreover, DPLPE (0.3-3 microg) or deltorphin (0.3-3 microg) failed to significantly affect the radiant heat-induced nociceptive responses. These results suggest that stimulation of delta1- and delta2-opioid receptors produces amnesia, depending on the learning tasks used.