Intraseptal infusion of oxotremorine impairs memory in a delayed-non-match-to-sample radial maze task. 2003

J G Bunce, and H R Sabolek, and J J Chrobak
Department of Psychology, University of Connecticut, Storrs, CT 06269, USA.

The medial septal nucleus is part of the forebrain circuitry that supports memory. This nucleus is rich in cholinergic receptors and is a putative target for the development of cholinomimetic cognitive-enhancing drugs. Septal neurons, primarily cholinergic and GABAergic, innervate the entire hippocampal formation and regulate hippocampal formation physiology and emergent function. Direct intraseptal drug infusions can produce amnestic or promnestic effects depending upon the type of drug administered. However, intraseptal infusion of the cholinomimetic oxotremorine has been reported to produce both promnestic and amnestic effects when administered prior to task performance. The present study examined whether post-acquisition intraseptal infusion of oxotremorine would be promnestic or amnestic in a delayed-non-match-to-sample radial maze task. In this task rats must remember information about spatial locations visited during a daily sample session and maintain that information over extended retention intervals (hours) in order to perform accurately on the daily test session. Treatments may then be administered during the retention interval. Alterations in maze performance during the test session an hour or more after treatment evidences effects on memory. In the present study, intraseptal infusion of oxotremorine (1.0-10.0 microg) produced a linear dose-related impairment of memory performance. Importantly, we also observed disrupted performance on the day after treatment. This persistent deficit was related only to memory over the retention interval and did not affect indices of short-term memory (ability to avoid repetitive or proactive errors during both the pre- and post-delay sessions). The persistent deficit contrasts with the acute amnestic effects of other intraseptally administered drugs including the cholinomimetics carbachol and tacrine. Thus, intraseptal oxotremorine produced a preferential disruption of memory consolidation as well as a persistent alteration of medial septal circuits. These findings are discussed with regards to multi-stage models of hippocampal-dependent memory formation and the further development of therapeutic strategies in the treatment of mild cognitive impairment as well as age-related decline and Alzheimer's dementia.

UI MeSH Term Description Entries
D008297 Male Males
D008569 Memory Disorders Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions. Memory Loss,Age-Related Memory Disorders,Memory Deficits,Memory Disorder, Semantic,Memory Disorder, Spatial,Memory Disorders, Age-Related,Retention Disorders, Cognitive,Semantic Memory Disorder,Spatial Memory Disorder,Age Related Memory Disorders,Age-Related Memory Disorder,Cognitive Retention Disorder,Cognitive Retention Disorders,Deficit, Memory,Deficits, Memory,Memory Deficit,Memory Disorder,Memory Disorder, Age-Related,Memory Disorders, Age Related,Memory Disorders, Semantic,Memory Disorders, Spatial,Memory Losses,Retention Disorder, Cognitive,Semantic Memory Disorders,Spatial Memory Disorders
D010095 Oxotremorine A non-hydrolyzed muscarinic agonist used as a research tool. Oxytremorine
D011930 Reaction Time The time from the onset of a stimulus until a response is observed. Response Latency,Response Speed,Response Time,Latency, Response,Reaction Times,Response Latencies,Response Times,Speed, Response,Speeds, Response
D004193 Discrimination Learning Learning that is manifested in the ability to respond differentially to various stimuli. Discriminative Learning,Discrimination Learnings,Discriminative Learnings,Learning, Discrimination,Learning, Discriminative
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004333 Drug Administration Routes The various ways of administering a drug or other chemical to a site in a patient or animal from where the chemical is absorbed into the blood and delivered to the target tissue. Administration Routes, Drug,Administration Route, Drug,Drug Administration Route,Route, Drug Administration,Routes, Drug Administration
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors

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