Cognitive performance of healthy young rats following chronic donepezil administration

Cutuli, Debora; Foti, Francesca; Mandolesi, Laura; Bartolo, Paola De; Gelfo, Francesca; Federico, Francesca; Petrosini, Laura

doi:10.1007/s00213-008-1084-0

Cited by 18 publications

(18 citation statements)

References 67 publications

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“…It is possible that the dose of donepezil was not optimal and that lower or higher doses would be more effective. Lower doses (≤1.0 mg/Kg/day) have been shown to enhance performance of young and aged rats on other spatial tasks including delayed visual matching to sample (Bennett, et al, 2006), Morris water maze (Cutuli, et al, 2008; Cutuli, et al, 2009; Hernandez, et al, 2006), object recognition (Prickaerts, et al, 2005), and radial arm maze (Cutuli et al, 2008; Cutuli et al, 2009) tasks. Donepezil at >1.0 mg/Kg has been shown to reduce impairments on a Morris water maze task in young rats treated with scopolamine (Takahata, et al, 2005), and in a rat model of encephalomyelitis (D’Intino, et al, 2005); however, not all studies have observed beneficial effects of donepezil on cognitive performance (Barnes et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Donepezil treatment restores the ability of estradiol to enhance cognitive performance in aged rats: Evidence for the cholinergic basis of the critical period hypothesis

Gibbs¹,

Mauk²,

Nelson³

et al. 2009

Hormones and Behavior

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Recent studies suggest that the ability of estradiol to enhance cognitive performance diminishes with age and/or time following loss of ovarian function. We hypothesize that this is due, in part, to a decrease in basal forebrain cholinergic function. This study tested whether donepezil, a cholinesterase inhibitor, could restore estradiol effects on cognitive performance in aged rats that had been ovariectomized as young adults. Rats were ovariectomized at 3 months of age, and then trained on a delayed matching to position (DMP) T-maze task, followed by a configural association (CA) operant condition task, beginning at 12-17 or 22-27 months of age. Three weeks prior to testing, rats started to receive either donepezil or vehicle. After one week, half of each group also began receiving estradiol. Acclimation and testing began seven days later and treatment continued throughout testing. Estradiol alone significantly enhanced DMP acquisition in middle-aged rats, but not in aged rats. Donepezil alone had no effect on DMP acquisition in either age group; however, donepezil treatment restored the ability of estradiol to enhance DMP acquisition in aged rats. This effect was due largely to a reduction in the predisposition to adopt a persistent turn strategy during acquisition. These same treatments did not affect acquisition of the CA task in middle-aged rats, but did have small but significant effects on response time in aged rats. The data are consistent with the idea that estrogen effects on cognitive performance are task specific, and that deficits in basal forebrain cholinergic function are responsible for the loss of estradiol effect on DMP acquisition in aged ovariectomized rats. In addition, the data suggest that enhancing cholinergic function pharmacologically can restore the ability of estradiol to enhance acquisition of the DMP task in very old rats following long periods of hormone deprivation. Whether donepezil has similar restorative effects on other estrogen-sensitive tasks needs to be explored.

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Section: Discussionmentioning

confidence: 99%

Donepezil treatment restores the ability of estradiol to enhance cognitive performance in aged rats: Evidence for the cholinergic basis of the critical period hypothesis

Gibbs¹,

Mauk²,

Nelson³

et al. 2009

Hormones and Behavior

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“…[27]. We previously demonstrated that healthy rats treated with donepezil during behavioral testing showed enhanced memory and explorative functions in RAM and OF, as well as reduced anxiety levels in EPM, but they did not exhibit any improvement in spatial span, motivational levels and associative learning [41]. Thus, although donepezil treatment during testing is able to improve cognitive performance even in unlesioned animals, donepezil treatment before testing (pre-treatment) exerts neuroprotective action only in the presence of lesion or insult.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of donepezil against cholinergic depletion

et al. 2013

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IntroductionIntraparenchymal injections of the immunotoxin 192-IgG-saporin into medial septum and nucleus basalis magnocellularis causes a selective depletion of basal forebrain cholinergic neurons. Thus, it represents a valid model to mimic a key component of the cognitive deficits associated with aging and dementia. Here we administered donepezil, a potent acetylcholinesterase inhibitor developed for treating Alzheimer’s disease, 15 days before 192-IgG-saporin injection, and thus we examined donepezil effects on neurodegeneration and cognitive deficits.MethodsCaspase-3 activity and cognitive performances of lesioned rats pre-treated with donepezil or saline were analyzed and compared to the outcomes obtained in pre-treated sham-lesioned rats.ResultsCholinergic depletion increased hippocampal and neocortical caspase-3 activity and impaired working memory, spatial discrimination, social novelty preference, and ultrasonic vocalizations, without affecting anxiety levels and fear conditioning. In lesioned animals, donepezil pre-treatment reduced hippocampal and neocortical caspase-3 activity and improved working memory and spatial discrimination performances and partially rescued ultrasonic vocalizations, without preventing social novelty alterations.ConclusionsPresent data indicate that donepezil pre-treatment exerts beneficial effects on behavioral deficits induced by cholinergic depletion, attenuating the concomitant hippocampal and neocortical neurodegeneration.

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“…In contrast, only a small number of studies have investigated the effects of donepezil on uncompromised rodents, although many of the reported effects of donepezil were similar. For instance, chronic administration of donepezil (0.5 mg/kg then 0.2 mg/kg) in uncompromised male rats was shown to enhance acquisition and performance on several spatial and nonspatial memory and attention tasks (Cutuli et al, 2008). Doses of 0.3 and 1 mg/kg of donepezil were also reported to decrease the number of errors emitted in a two-phase radial-arm maze procedure compared to control in male rats (Wise et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Gonadal hormones modulate the potency of the disruptive effects of donepezil in male rats responding under a nonspatial operant learning and performance task

Leonard

Hearn²,

Catling³

et al. 2010

Behavioural Pharmacology

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Cognitive performance of healthy young rats following chronic donepezil administration

Abstract: The present findings show the specific profile of donepezil action on cognitive functions in the presence of unaltered cholinergic neurotransmission systems.

Cited by 18 publications

References 67 publications

Donepezil treatment restores the ability of estradiol to enhance cognitive performance in aged rats: Evidence for the cholinergic basis of the critical period hypothesis

Donepezil treatment restores the ability of estradiol to enhance cognitive performance in aged rats: Evidence for the cholinergic basis of the critical period hypothesis

Neuroprotective effects of donepezil against cholinergic depletion

Gonadal hormones modulate the potency of the disruptive effects of donepezil in male rats responding under a nonspatial operant learning and performance task

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