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Minaprine improves impairment of working memory induced by scopolamine and cerebral ischemia in rats
T Yamamoto1, S Yatsugi, M Ohno
1Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Abstract:
Using a repeated acquisition procedure in a three-panel runway apparatus, the effects of minaprine on the impairment of working memory produced by scopolamine, ethylcholine aziridinium ion (AF64A) or cerebral ischemia were investigated in rats. Minaprine (3.2-32 mg/kg IP) as well as idebenone (10-100 mg/kg IP) and physostigmine (0.1-0.32 mg/kg IP) dose-dependently reduced the increase of errors (pushes made on the two incorrect panels located at each choice point) induced by 0.56 mg/kg IP scopolamine. Cerebral ischemia for 5 min caused a significant increase of errors in the runway task. Minaprine at 3.2 and 10 mg/kg administered IP immediately after blood recirculation and again 30 min before the runway test conducted 24 h after ischemia, significantly reduced increases in errors expected to occur after 5 min of ischemia. Physostigmine 0.1 mg/kg similarly attenuated the increase in errors in ischemic rats. However, minaprine at doses up to 32 mg/kg IP failed to reduce the increase of errors induced by AF64A 2.5 nmol injected into the dorsal hippocampus. These findings suggest that minaprine exerts an ameliorating effect on amnesia produced by scopolamine and cerebral ischemia, probably through mediation of its stimulant action on central cholinergic systems.
Insights
Minaprine, a stimulant drug, improved working memory in rats impaired by scopolamine or cerebral ischemia. However, it did not reverse memory deficits caused by ethylcholine aziridinium ion (AF64A).
Area of Science:
- Neuroscience
- Pharmacology
- Cognitive Science
Background:
- Working memory impairment is a significant challenge in neurological disorders.
- Scopolamine, AF64A, and cerebral ischemia are common models to study memory deficits.
- Minaprine is a drug with potential cognitive-enhancing properties.
Purpose of the Study:
- To investigate the effects of minaprine on working memory impairment induced by scopolamine, AF64A, and cerebral ischemia in rats.
- To compare minaprine's efficacy with other cognitive enhancers like idebenone and physostigmine.
- To explore the potential mechanisms underlying minaprine's effects on memory.
Main Methods:
- A repeated acquisition procedure in a three-panel runway apparatus was used.
- Rats received minaprine, idebenone, or physostigmine after induction of memory impairment.
- Memory performance was assessed by measuring errors in the runway task.
Main Results:
- Minaprine, idebenone, and physostigmine dose-dependently reduced scopolamine-induced working memory errors.
- Cerebral ischemia significantly increased errors, an effect attenuated by minaprine and physostigmine.
- Minaprine failed to improve memory deficits induced by AF64A in the dorsal hippocampus.
Conclusions:
- Minaprine demonstrates therapeutic potential for memory impairments associated with scopolamine and cerebral ischemia.
- The drug's effects may be mediated by its stimulant action on central cholinergic systems.
- Minaprine's efficacy is specific to certain types of memory impairment, not universally effective.
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