Differential effects of posterior septal lesions on dispositional and representational memory.

Thomas, Garth J.; Gash, Don M.

doi:10.1037/0735-7044.100.5.712

Cited by 37 publications

(16 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…192 IgG-saporin produced consistent deficits in performance of the paired-run alternation task, with animals performing at essentially chance levels. The data are consistent with an involvement of the basal forebrain cholinergic system in representational memory function [Thomas and Gash, 1986;Messer et al, 1991]. Furthermore, the ability of xanomeline and CDD-0102 to completely reverse memory deficits produced by 192 IgG-saporin provides further support for the hypothesis that M 1 muscarinic receptors are involved in representational memory function [Messer et al, , 1991.…”

Section: Discussionsupporting

confidence: 76%

“…The paired-run alternation task assessed representational memory function, which is dependent on cues not available at the time of choice [Thomas and Spafford, 1984;Thomas and Gash, 1986]. 192 IgG-saporin produced consistent deficits in performance of the paired-run alternation task, with animals performing at essentially chance levels.…”

Section: Discussionmentioning

confidence: 99%

“…The behavioral methods were modified from procedures outlined by Thomas and colleagues [Thomas and Spafford, 1984;Thomas and Gash, 1986]. The paradigm provides a measure of representational memory; that is, the ability to recall information based on cues not present at the time of choice.…”

Section: Representational Memory Taskmentioning

confidence: 99%

See 2 more Smart Citations

Development of CDD‐0102 as a selective M₁ agonist for the treatment of Alzheimer's disease

Messer

Bachmann

Dockery

et al. 2002

Drug Development Research

View full text Add to dashboard Cite

Selective muscarinic agonists might be useful in the treatment of Alzheimer's disease. To help characterize the activity and functional selectivity of two M 1 muscarinic agonists, secretion of amyloid precursor protein, brain penetration, side effect profiles, cognition-enhancing properties, oral bioavailability, and acute toxicity were evaluated. CDD-0102 stimulated the secretion of APP from CHO-K1 cells expressing M 1 receptors and penetrated into the brain following i.p. administration in rodents. CDD-0102 produced relatively few cholinergic side effects (e.g., diarrhea, salivation) following i.p. administration in mice. The effects of muscarinic agonists on memory function were examined following bilateral injections of 192 IgG-saporin into the diagonal band of rats to lesion basal forebrain cholinergic pathways. 192 IgG-saporin produced decreases in cortical and hippocampal choline acetyltransferase activity and impaired performance of a paired-run, delayed-alternation task in a T-maze relative to vehicle-injected controls. Toxin-treated rats performed significantly better following i.p. injections (1 mg/kg) of either xanomeline or CDD-0102 as compared with saline. Prominent cholinergic side effects (e.g., diarrhea) were apparent only following xanomeline treatments. In separate studies, oral administration of CDD-0102 (10 mg/kg) reversed the memory deficits induced by 192 IgG-saporin in the T-maze task. Rats achieved 54 7 4.2% correct choices with saline, but 94 7 1.2% following CDD-0102 injection. In acute toxicity studies in mice, the LD 50 of CDD-0102 was greater than 1,000 mg/kg orally; 190 mg/kg i.p. The LD 50 of xanomeline was 100 mg/kg p.o. and 75 mg/kg i.p. In summary, both xanomeline and CDD-0102 displayed beneficial effects on memory function, while CDD-0102 also exhibited a low side effect profile and low toxicity. CDD-0102 warrants further evaluation as a therapeutic agent for the treatment of Alzheimer's disease. Drug Dev.

show abstract

Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Development of CDD‐0102 as a selective M₁ agonist for the treatment of Alzheimer's disease

Messer

Bachmann

Dockery

et al. 2002

Drug Development Research

View full text Add to dashboard Cite

show abstract

“…He reinforced his view by adding that there are extensive connections between the hippocampus and the sensory and multimodal association cortex in nonhuman primates [16,27,28,31]. …”

Section: Figmentioning

confidence: 99%

“…On the other hand, their dispositional memory seemed unaffected, as they could still remember the behavioral significance of the discriminative cues in the maze [24,25,26]. Another approach that Thomas pursued was hippocampectomy, which led to distinct results for the 2 types of memory: Thomas and Gash [27,28,29] observed that hippocampectomy had disastrous effects on representational memory, whereas dispositional memory was only temporarily affected.…”

Section: Figmentioning

confidence: 99%

Garth J. Thomas, Physiological Psychologist: An Appraisal of His Contributions to Memory Research

Tzouma

Triarhou²

2017

Ann Neurosci

View full text Add to dashboard Cite

This note is a tribute to Garth J. Thomas (1916-2008), late Professor of Brain Research at the University of Rochester, New York. Thomas was an influential psychologist, albeit for his research in learning and memory, as much as for his work as editor of the Journal of Comparative and Physiological Psychology. In his studies, he combined experimental lesions with behavioral analyses. He introduced the terms “dispositional” and “representational” to describe the 2 different types of memory function, and emphasized that memory must be studied not only through behavioristic psychology, but also in a molecular and physiological context. Through his experimentation in rodents, Thomas concluded that distinct neural mechanisms underpin dispositional and representational memory. Prompted by Thomas' remarks on the future evolution of research techniques, we touch upon some ideas on the engram and the glial theory in a modern perspective.

show abstract

Tetrahydropyrimidine derivatives display functional selectivity for M1 muscarinic receptors in brain

et al. 1997

View full text Add to dashboard Cite

Selective muscarinic agonists might be useful in the treatment of Alzheimer's disease. Previous studies identified several amidine derivatives as selective and efficacious m1 agonists, using muscarinic receptor subtypes expressed in cell lines. In the present studies, the functional selectivities, side effect profiles and memory‐enhancing properties of these ligands were examined through a series of in vitro and in vivo experiments. CDD‐0078, CDD‐0097, and CDD‐0102 behaved as partial agonists by stimulating PI turnover in rat cortical slices to roughly 100% above basal levels. Pirenzepine was more potent than either AF‐DX 116 or p‐F‐hexahydrosiladifenidol (p‐F‐HHSiD) in blocking the PI responses of each ligand, suggesting that the responses were due to activation of M1 receptors. The time course of pharmacological responses was examined following i.p. injections of muscarinic agonists. Low does (0.1 and 1.0 mg/kg) of CDD‐0078, CDD‐0097, and CDD‐0102 did not elicit signs of cholinergic activity during the 2‐hr testing period. The highest dose tested (10 mg/kg) produced a modest degree of salivation and lacrimation during the first 30‐min period. Core body temperature remained unaffected. Central nervous system (CNS) penetration was evaluated through ex vivo binding studies. CDD‐0097 inhibited 1.0 nM [3H]pirenzepine binding in a dose‐dependent manner 30 min following i.p. injections. In behavioral studies, CDD‐0097 (1.0 mg/kg) completely reversed the memory deficits induced by hemicholinium‐3 or by IgG‐192 saporin in two types of memory tasks. It did not impair the performance of control animals in either task. In summary, CDD‐0097 displayed a limited side‐effect profile and the ability to penetrate into the central nervous system and stimulate M1 receptors. The amidine derivatives should be useful in further exploring the functional consequences of activating M1 muscarinic receptors in the CNS. The beneficial effects of CDD‐0097 on memory function warrant further examination of the compound as a selective M1 agonist for the treatment of Alzheimer's disease. Drug Dev. Res. 40:171–184, 1997. © 1997 Wiley‐Liss, Inc.

show abstract

Differential effects of posterior septal lesions on dispositional and representational memory.

Cited by 37 publications

References 14 publications

Development of CDD‐0102 as a selective M₁ agonist for the treatment of Alzheimer's disease

Development of CDD‐0102 as a selective M₁ agonist for the treatment of Alzheimer's disease

Garth J. Thomas, Physiological Psychologist: An Appraisal of His Contributions to Memory Research

Tetrahydropyrimidine derivatives display functional selectivity for M1 muscarinic receptors in brain

Contact Info

Product

Resources

About

Differential effects of posterior septal lesions on dispositional and representational memory.

Cited by 37 publications

References 14 publications

Development of CDD‐0102 as a selective M1 agonist for the treatment of Alzheimer's disease

Development of CDD‐0102 as a selective M1 agonist for the treatment of Alzheimer's disease

Garth J. Thomas, Physiological Psychologist: An Appraisal of His Contributions to Memory Research

Tetrahydropyrimidine derivatives display functional selectivity for M1 muscarinic receptors in brain

Contact Info

Product

Resources

About

Development of CDD‐0102 as a selective M₁ agonist for the treatment of Alzheimer's disease

Development of CDD‐0102 as a selective M₁ agonist for the treatment of Alzheimer's disease