Insulin potentiates the therapeutic effect of memantine against central STZ-induced spatial learning and memory deficit

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Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. Memantine has been approved for moderate to severe AD, but evidence indicates that it does not modify disease progression. Recently insulin has been found to exert some beneficial effects on cognition. This study aimed to compare the protective effects of memantine and insulin in an animal model of memory deficit. It also evaluated the effects of combination therapy of these drugs. Adult male Sprague-Dawely rats approximately 8–10 weeks old were used. The canules were implanted bilaterally into lateral ventricles. STZ was administered on days 1 and 3 (3 mg/kg in divided doses) and Memantine (5 or 10 mg/kg/ip) or/and Insulin (3 or 6 mU/icv) were started from day 4 and continued till day 13. The animal's learning and memory capability was assessed on days 14–16 using Morris water maze. On day 17 a visible platform test was done to assess the animals' visuomotor ability. After completion of behavioral studies the brain sections were stained with hematoxylin and eosin for routine histological evaluation. The results show that memantine in doses 5 and 10 mg/kg improved memory at day 3 of training and memantine 5 mg/kg was more potent than memantine 10 mg/kg.

Insulin in dose 3mU, but not 6 mU, reversed STZ-induced memory deficit from day 2 of training. When insulin was added to memantine, it increased the potency of memantine 5 mg/kg in preventing a memory deficit, but surprisingly was not successful in impeding STZ-induced amnesia, in combination with memantine 10 mg/kg. This research work revealed that insulin act more efficiently than memantine in reversing STZ-induced memory impairment. Additionally combination of insulin and memantine seems to act better than memantine alone, providing that a dose adjustment has been done. This study suggests considering the combination therapy of memantine and insulin in dementia and AD.

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