Effects of selegiline alone or with donepezil on memory impairment in rats

Takahata, Kazue; Minami, Anzu; Kusumoto, Haruko; Shimazu, Seiichiro; Yoneda, Fumio

doi:10.1016/j.ejphar.2005.06.024

Cited by 33 publications

(18 citation statements)

References 31 publications

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“…Beneficial effects have been reported in preclinical models in which donepezil was administered in combination with other putative cognitive enhancers. Concomitant administration of donepezil and selegiline, a monoamine oxidase-B inhibitor, reversed memory deficits in the Morris water maze induced by the administration of scopolamine or p-chlorophenylalanine at doses of these agents not found to reverse memory deficits when given alone (Takahata et al, 2005). Administration of donepezil and FK960, a putative cognitive enhancer of piperazine derivation that is thought to enhance somatostatin release in the hippocampus, at doses found to have no effect when given alone improved learning impairments in a passive avoidance task induced by lesions of the nucleus basalis magnocellularis (Tokita et al, 2002).…”

Section: Discussionmentioning

confidence: 95%

“…The high concentration of CB 1 receptors (Herkenham et al, 1991) and the presence of anandamide and 2-AG in the hippocampus and other forebrain regions associated with memory function (Felder et al, 1996;Di Marzo et al, 2000) are consistent with the notion that the endocannabinoid system modulates cognitive processes. Administration of the CB 1 receptor antagonist rimonabant (SR 141716) (Rinaldi-Carmona et al, 1995) has been reported to enhance memory in delayed radialarm maze tasks (Lichtman, 2000;Wolff and Leander, 2003), a social recognition memory paradigm (Terranova et al, 1996), and an elevated T-maze task (Takahata et al, 2005). Interestingly, intrahippocampal administration of rimonabant in food-storing birds enhanced memory for the location of a hidden food reward (Shiflett et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Combination of Rimonabant and Donepezil Prolongs Spatial Memory Duration

Wise

Iredale

Stokes

et al. 2007

Neuropsychopharmacol

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The observations that the cannabinoid 1 (CB 1 ) receptor antagonist/inverse agonist, rimonabant, and the selective noncompetitive inhibitor of acetylcholinesterase (AChE), donepezil, improve performance in a variety of animal memory models, suggest that these neurochemical systems play integral roles in cognition. The present study tested whether each of these agents administered alone or in combination will prolong the duration of spatial memory. Rats were trained in a two-phase radial-arm maze procedure, consisting of acquisition and retrieval tests, which were separated by an 18 h delay. Each drug was administered 30 min before the acquisition phase, immediately after the acquisition phase, or 30 min before the retrieval test to assess acquisition/consolidation, consolidation, and retrieval mnemonic processes, respectively. Rimonabant or donepezil administered before the acquisition phase, but not immediately after acquisition or before retrieval, led to a significant decrease in the number of errors committed during the retrieval test. Combined administration of subthreshold doses of rimonabant and donepezil that had no discernable effects on performance when given alone, enhanced memory.These results taken together demonstrate that the delay radial-arm maze task is sufficiently sensitive to detect memory enhancing effects of these drugs. Moreover, these findings suggest that combined administration of subthreshold doses of rimonabant and donepezil can improve memory and may represent a novel approach to treat cognitive deficits associated with neurodegenerative disorders.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Combination of Rimonabant and Donepezil Prolongs Spatial Memory Duration

Wise

Iredale

Stokes

et al. 2007

Neuropsychopharmacol

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“…Administration of either drug alone improved spatial and associative memory. Both drugs used together at doses that are not individually efficacious improved memory, indicating that deprenyl potentiated the effect of donepezil on cognition (407,418). Additional studies have shown that deprenyl has longterm beneficial effects in AD on memory modalities that require prefrontal areas of the brain, which are rich in dopamine receptors.…”

Section: Fig 4 Production Of Superoxide By Mitochondriamentioning

confidence: 97%

Reactive Oxygen Species in the Regulation of Synaptic Plasticity and Memory

Massaad

Klann

2011

Antioxidants & Redox Signaling

493

350

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The brain is a metabolically active organ exhibiting high oxygen consumption and robust production of reactive oxygen species (ROS). The large amounts of ROS are kept in check by an elaborate network of antioxidants, which sometimes fail and lead to neuronal oxidative stress. Thus, ROS are typically categorized as neurotoxic molecules and typically exert their detrimental effects via oxidation of essential macromolecules such as enzymes and cytoskeletal proteins. Most importantly, excessive ROS are associated with decreased performance in cognitive function. However, at physiological concentrations, ROS are involved in functional changes necessary for synaptic plasticity and hence, for normal cognitive function. The fine line of role reversal of ROS from good molecules to bad molecules is far from being fully understood. This review focuses on identifying the multiple sources of ROS in the mammalian nervous system and on presenting evidence for the critical and essential role of ROS in synaptic plasticity and memory. The review also shows that the inability to restrain either age-or pathology-related increases in ROS levels leads to opposite, detrimental effects that are involved in impairments in synaptic plasticity and memory function.

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“…Early studies with the centrally acting cholinesterase inhibitor physostigmine demonstrated consistent but partial reversal of scopolamine-induced memory deficits (Bartus 1978;Mewaldt and Ghoneim 1978). More recent studies with the currently prescribed AD drugs rivastigmine, donepezil, and galantamine have reported similar scopolamine-reversal properties in the rat (Bejar et al 1999;Takahata et al 2005;van der Staay and Bouger 2005;de Bruin and Pouzet 2006;Lindner et al 2006). However, cholinomimetic drugs are not the only pharmacological class to reverse scopolamine-induced memory deficits (Misane and Ogren 2003;Van Kampen et al 2004;Lieben et al 2005) attesting perhaps to the greater than expected versatility of the model.…”

Section: Introductionmentioning

confidence: 99%

The scopolamine-reversal paradigm in rats and monkeys: the importance of computer-assisted operant-conditioning memory tasks for screening drug candidates

et al. 2007

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Rationale The scopolamine-reversal model is enjoying a resurgence of interest in clinical studies as a reversible pharmacological model for Alzheimer's disease (AD). The cognitive impairment associated with scopolamine is similar to that in AD. The scopolamine model is not simply a cholinergic model, as it can be reversed by drugs that are noncholinergic cognition-enhancing agents. Objectives The objective of the study was to determine relevance of computer-assisted operant-conditioning tasks in the scopolamine-reversal model in rats and monkeys. Materials and methods Rats were evaluated for their acquisition of a spatial reference memory task in the Morris water maze. A separate cohort was proficient in performance of an automated delayed stimulus discrimination task (DSDT). Rhesus monkeys were proficient in the performance of an automated delayed matching-to-sample task (DMTS). Results The AD drug donepezil was evaluated for its ability to reverse the decrements in accuracy induced by scopolamine administration in all three tasks. In the DSDT and DMTS tasks, the effects of donepezil were delay (retention interval)-dependent, affecting primarily short delay trials. Donepezil produced significant but partial reversals of the scopolamine-induced impairment in task accuracies after 2 mg/kg in the water maze, after 1 mg/kg in the DSDT, and after 50 μg/kg in the DMTS task. Conclusions The two operant-conditioning tasks (DSDT and DMTS) provided data most in keeping with those reported in clinical studies with these drugs. The model applied to nonhuman primates provides an excellent transitional model for new cognition-enhancing drugs before clinical trials.

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Effects of selegiline alone or with donepezil on memory impairment in rats

Cited by 33 publications

References 31 publications

Combination of Rimonabant and Donepezil Prolongs Spatial Memory Duration

Combination of Rimonabant and Donepezil Prolongs Spatial Memory Duration

Reactive Oxygen Species in the Regulation of Synaptic Plasticity and Memory

The scopolamine-reversal paradigm in rats and monkeys: the importance of computer-assisted operant-conditioning memory tasks for screening drug candidates

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