Involvement of delta1-opioid receptors in the spatial learning impairment in streptozotocin-induced diabetic mice.

It is well accepted that diabetes leads to learning and memory impairment in humans and rodents. Because central delta-opioid receptors have important roles in learning processes, we investigated the involvement of delta-opioid receptors in the spatial learning impairment in streptozotocin (STZ)-induced diabetic mice by the Morris water maze test. The escape latencies to the platform were significantly increased in diabetic mice without changes in the ability to swim. The delta1/delta2-opioid receptor antagonist naltrindole (1 mg/kg/day, s.c.) slightly, but not significantly, reduced the escape latencies in diabetic mice. The selective delta1-opioid receptor antagonist 7-benzylidenenaltrexone (0.3 and 1 mg/kg/day, s.c.), but not the selective delta2-opioid receptor antagonist naltriben (0.3 and 1 mg/kg/day, s.c.), significantly reduced the escape latencies in diabetic mice. These antagonists had no effect on the escape latencies in non-diabetic mice. The selective delta1-opioid receptor agonist [D-Pen2, D-Pen5]-enkephalin (10 nmol/mouse/day, i.c.v.) significantly increased the escape latencies in both non-diabetic and diabetic mice. Based on these results, we suggest that the enhanced response to central delta1-opioid receptors in diabetic mice is involved, at least in part, in the spatial learning impairment in the Morris water maze test.