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.
Kamei
Junzo
J
Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-16 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Miyata
Shigeo
S
Takahashi
Masashi
M
Saitoh
Akiyoshi
A
D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004745:Enkephalins / Q000494:pharmacology; D004924:Escape Reaction / Q000187:drug effects; D051379:Mice; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000502:physiology*; D013028:Space Perception / Q000502:physiology*
D001597:Benzylidene Compounds; D004745:Enkephalins; D017465:Receptors, Opioid, delta; C068868:naltrindole benzofuran; C077358:7-benzylidenenaltrexone; D009271:Naltrexone; C055382:naltrindole