Dose-response differences in the ability of ramipril to improve retention in diabetic mice.
Ramipril blocks the conversion of angiotensin I to II. The literature indicates that diabetes is often associated with mild impairment of learning and memory. The study reports the effects of ramipril on memory retention in diabetic and non-diabetic mice. Mice were made diabetic by an injection of streptozocin. After overt signs of diabetes were present, diabetic or vehicle-treated mice were partially trained on a footshock active avoidance task. Immediately after training, ramipril (0.5-1.5 mg/kg s.c.) was administered and retention was tested by continuing training one week later until mice avoided footshock on five out of six trails. The results indicate that ramipril enhanced retention of both diabetic and control mice but it required about 5 times as much ramipril in diabetic as control mice to achieve the same effect on retention. Increased sensitivity to angiotensin II may play a role in cognitive impairment in diabetes.
Flood
J F
JF
Geriatric Research, Education and Clinical Center (GRECC), Veterans Administration Medical Center, St. Louis, MO 63106.
Morley
J E
JE
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000523:psychology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D017257:Ramipril / Q000494:pharmacology*; D012153:Retention, Psychology / Q000187:drug effects*
D000804:Angiotensin II; D000803:Angiotensin I; D017257:Ramipril