Dose-specific effects of scopolamine on canine cognition: Impairment of visuospatial memory, but not visuospatial discrimination

Araujo, Joseph A.; Chan, Alan; Winka, L. L.; Seymour, Patricia A.; Milgram, Norton W.

doi:10.1007/s00213-004-1777-y

Cited by 34 publications

(25 citation statements)

References 50 publications

(61 reference statements)

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“…The scopolamine model is frequently used in preclinical studies of cognitive impairment. Studies in animals showed that scopolamine induced memory impairments similar to those seen in humans [11][12][13]. Scopolamine has been used in humans for several different purposes, e.g.…”

Section: Introductionmentioning

confidence: 98%

Pharmacokinetic–pharmacodynamic relationships of central nervous system effects of scopolamine in healthy subjects

Liem-Moolenaar

Boer²,

Timmers³

et al. 2011

Brit J Clinical Pharma

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Scopolamine affected different CNS functions in a concentration-dependent manner, which based on their distinct PK-PD characteristics seemed to reflect multiple distinct functional pathways of the cholinergic system. All PD effects showed considerable albeit variable delays compared with plasma concentrations. The t(1/2) k(eo) of the central effects was longer than of the peripheral effects on heart rate, which at least partly reflects the long CNS retention of scopolamine, but possibly also the triggering of independent secondary mechanisms. PK-PD analysis can optimize scopolamine administration regimens for future research and give insight into the physiology and pharmacology of human cholinergic systems.

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Section: Introductionmentioning

confidence: 98%

Pharmacokinetic–pharmacodynamic relationships of central nervous system effects of scopolamine in healthy subjects

Liem-Moolenaar

Boer²,

Timmers³

et al. 2011

Brit J Clinical Pharma

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“…Previously we provided evidence of cholinergic involvement in canine cognition by examining the effect of scopolamine on performance of a delayed non-matching to position task (DNMP) and found working memory performance in aged dogs was disrupted by a 15 μg/kg dose of scopolamine, which produced no obvious behavioral effects [49]. By contrast, young dogs were not impaired by the same scopolamine dose [50] and showed higher muscarinic receptor density than aged dogs [51].…”

Section: Introductionmentioning

confidence: 99%

Cholinesterase Inhibitors Improve Both Memory and Complex Learning in Aged Beagle Dogs

Araujo

Greig

Ingram

et al. 2011

JAD

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Similar to patients with Alzheimer’s disease (AD), dogs exhibit age-dependent cognitive decline, amyloid-β (Aβ) pathology, and evidence of cholinergic hypofunction. The present study sought to further investigate the role of cholinergic hypofunction in the canine model by examining the effect of the cholinesterase inhibitors phenserine and donepezil on performance of two tasks, a delayed non-matching-to-position task (DNMP) designed to assess working memory, and an oddity discrimination learning task designed to assess complex learning, in aged dogs. Phenserine (0.5 mg/kg; PO) significantly improved performance on the DNMP at the longest delay compared to wash-out and partially attenuated scopolamine-induced deficits (15 μg/kg; SC). Phenserine also improved learning on a difficult version of an oddity discrimination task compared to placebo, but had no effect on an easier version. We also examined the effects of three doses of donepezil (0.75, 1.5, and 6 mg/kg; PO) on performance of the DNMP. Similar to the results with phenserine, 1.5 mg/kg of donepezil improved performance at the longest delay compared to baseline and wash-out, indicative of memory enhancement. These results further extend the findings of cholinergic hypofunction in aged dogs and provide pharmacological validation of the canine model with a cholinesterase inhibitor approved for use in AD. Collectively, these studies support utilizing the aged dog in future screening of therapeutics for AD, as well as for investigating the links among cholinergic function, Aβ pathology, and cognitive decline.

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“…The P2 delay was also induced in normal subjects by the administration with anti-cholinergic drugs [2]. Araujo et al [1] demonstrated that the cholinergic system was also important in cognitive deficits in dogs. Therefore, the delay of the latency of P2 and the later peaks observed in aged dogs might be reflected the neurological disturbance with the defects of neurotransmitter.…”

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confidence: 98%

Age-Associated Changes of Flash Visual Evoked Potentials in Dogs

Kimotsuki¹,

Yasuda

Tamahara

et al. 2006

The Journal of Veterinary Medical Science

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ABSTRACT. Age-associated changes of visual evoked potentials by flash stimulation (flash VEP) were evaluated in 53 beagle dogs aged from 1-to 15-year-old. Among the components of flash VEP consisted of 3 positive (P1, P2 and P3) and 2 negative (N1 and N2) peaks by 150 msec, the latency of P2 and the later peaks (N2 and P3) were significantly delayed with aging. Both amplitudes of the P2-N2 and N2-P3 also showed a significant correlation with aging. The flash VEP is considered to be an available and useful technique to evaluate not only for visual pathway, but also some disturbance of neurological functions, like as those reported in demented human. KEY WORDS: age-associated change, canine, flash VEP.J. Vet. Med. Sci. 68(1): 79-82, 2006 Visual evoked potentials (VEPs) indicated electrophysiological responses from retina to visual cortex is reported to be an useful technique for evaluating optic pathway [8] and also to be a sensitive indicator for dementia in human [4,18,22]. Visser et al. [21] demonstrated that the latency of the flash VEP components was delayed in the patients with dementia, especially Alzheimer's disease. The latency of the positive peak 2 (P2 :mean latency was 100 msec) and the later components were significantly delayed, although the similar results were sometimes detected in aged human. The flash VEP recorded in dogs showed 3 positive (P1, P2 and P3) and 2 negative (N1 and N2) components by 150 msec after the flash stimuli, like as those reported in human [11,17,19]. In addition, various age-associated pathological and/or physiological changes were commonly observed in aged dogs as well as aged human [5,10]. Since there are few diagnostic techniques for dementia in dogs, age-associated changes of the flash VEP were evaluated using various aged beagle dogs.Total 53 beagle dogs (25 male and 28 female) aged from 1-to 15-year-old kept in Medical Safety Research Laboratories, Sankyo Co., Ltd., were used.The flash VEP was recorded using needle electrodes inserted in the midline of the scalp according to the method reported by Strain et al. [18]. Briefly, electrodes of recording, reference, and ground were placed over the midline of the nuchal crest, forehead, and vertex, respectively. Prior to recording, the dogs were instilled the mydriatic drug, including tropicamide and phenylephrine hydrochloride, and subcutaneously given atropine sulfate (0.05 mg/kg) and intramuscularly given xylazine (2-3 mg/kg) for the sedation. Then the dogs were dark-adapted at least 1 hr and the flash VEP were recorded in the dark shielded room. The white flash stimulus was given 1/sec with the intensity of 0.6 joule using a photostimulator (SLS-3100 Photostimulator, Nihon Kohden Co., Tokyo, Japan). The xenon lamp was located about 15 cm in front of the examined eye and another eye was covered with the black cloth. The responses were recorded with signal averager (Neuropack Four Mini, Nihon Kohden Co, Tokyo, Japan). The bandpass filter was set at 1 Hz low and 1,000 Hz high. In this study, consecutive 30 responses wer...

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Dose-specific effects of scopolamine on canine cognition: Impairment of visuospatial memory, but not visuospatial discrimination

Cited by 34 publications

References 50 publications

Pharmacokinetic–pharmacodynamic relationships of central nervous system effects of scopolamine in healthy subjects

Pharmacokinetic–pharmacodynamic relationships of central nervous system effects of scopolamine in healthy subjects

Cholinesterase Inhibitors Improve Both Memory and Complex Learning in Aged Beagle Dogs

Age-Associated Changes of Flash Visual Evoked Potentials in Dogs

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