1994 Fiscal Year Final Research Report Summary
Developmental study of newly-synthesized peptidergic nootropics for Alzheimer-type senile dementia
| Project/Area Number |
05454582
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Meijo University |
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Principal Investigator |
KAMEYAMA Tsutomu Department of Chemical Pharmacology Faculty of Pharmaceutical Sciences Meijo Uiversity Professor, 薬学部, 教授 (10076698)
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| Co-Investigator(Kenkyū-buntansha) |
HIRAMATSU Masayuki Department of Chemical Pharmacology Faculty of Pharmaceutical Sciences Meijo Uni, 薬学部, 助手 (10189863)
UKAI Makoto Department of Chemical Pharmacology Faculty of Pharmaceutical Sciences Meijo Uni, 薬学部, 助教授 (80131209)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Dynorphin / Alzheimer-type senile dementia / Passive avoidance learning / Galanin / Nor-binaltorphimine / Physostigmine |
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| Research Abstract |
The present study examined the effects of intracerebroventricular injection of dynorphin A- (1-13) and galanin on memory processes by using the passive avoidance task in mice. The middle doses (0.3 and 1 mu g) of galanin significantly decreased step-down latency of passive avoidance response when given 15 min before retention tests. Physostigmine (0.2 mg/kg), a cholinesterase inhibitor, and oxotremorine (0.01 and 0.03 mg/kg), a cholinergic receptor agonist, significantly inhibited the shotening of step-down latency induced by galanin (0.3 mu g) administered 15 min before retention tests, indicating the involvement of cholinergic dysfunction in the galanin (0.3 mu g) -induced shortening of step-down latency. Although dynorphin A- (1-13) (1 or 3 mu g) did not prolong the step-down latency induced by weaker electroshocks, it inhibited the galanin (0.3 mu g) -induced shortening of step-down latency. The effects of dynorphin A- (1-13) (3mu g) on the galanin-induced shortening of step-down latency were almost completely reversed by pretreatment with nor-binaltorphimine (4 mu g), a kappa-selective opioid receptor antagonist. These results strongly suggest that dynorphin A- (1-13) attenuates galanin-induced impairment of memory processes through the mediation of kappa-opioid receptors.
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