Cholinesterase Inhibition in the Scopolamine Model of Dementia

Wesnes, Keith; Simpson, P. M.; White, Linda R.; Pinker, Sally; Jertz, Gabriela; Murphy, Michael R.; Siegfried, Klaudius

doi:10.1111/j.1749-6632.1991.tb00231.x

Cited by 55 publications

(24 citation statements)

References 13 publications

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“…Similar eects have also been reported by other investigators (Frey et al, 1992;Preston et al, 1989;Sloan et al, 1992;Wesnes, 1988). The impairments observed in conjunction with scopolamine also resemble many of the de®cits identi®ed in patients with Alzheimer's disease (Wesnes et al, 1991). It appears that the amnesia induced by scopolamine is due to a speci®c disruption of cholinergic mechanisms (Bartus et al, 1982).…”

Section: Discussionsupporting

confidence: 61%

“…0 mg physostigmine was administered together with 0 . 5 mg scopolamine s.c. (Wesnes et al, 1991). Indeed, in the present study the eects of physostigmine were not evaluated on their own.…”

Section: Discussionmentioning

confidence: 85%

“…Animal and human studies suggest that an impairment of cholinergic neurotransmission and a loss of muscarinic receptors in the CNS may be one of the causes of memory de®cits seen early in the course of Alzheimer's disease (Bartus, 1978;Bartus, 1979;Bartus et al, 1980;Deutsch, 1971;Drachmann et al, 1974;Wesnes et al, 1991). One model based on this`cholinergic hypothesis' of geriatric memory loss is provided by the use of scopolamine (Whitehouse et al, 1981).…”

Section: Introductionmentioning

confidence: 98%

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Effects of physostigmine on scopolamine-induced changes in quantitative electroencephalogram and cognitive performance

Ebert

Oertel

Wesnes³

et al. 1998

Hum. Psychopharmacol. Clin. Exp.

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The eects of physostigmine on scopolamine-induced changes were investigated in a randomized, double-blind crossover study utilizing quantitative electroencephalogram (qEEG) and cognitive tasks. Ten healthy male volunteers received scopolamine 0 . 6 mg subcutaneously. After 90 min, single doses of either 0 . 5, 1 . 0 and 2 . 0 mg physostigmine salicylate or placebo were administered subcutaneously in randomized order. qEEG, cognitive function and the visual analogue scale were recorded before and at 1, 2, 3, 4, 6, and 8 h after scopolamine administration; that was 0 . 5, 1 . 5, 2 . 5, 4 . 5, and 6 . 5 h after physostigmine administration. Scopolamine produced an increase in delta (1 . 25±4 . 50 Hz) and theta power (4 . 75±6 . 75 Hz) in qEEG 1 h after administration compared to baseline, while physostigmine decreased the spectral delta power density in qEEG compared to placebo. The maximal eect of physostigmine was seen up to 1 . 5 h after injection. A dose-dependent reversal of the scopolamine induced decrements in cognitive performance was found 0 . 5 h after administration of physostigmine. Psychometric tests sensitively discriminated between the doses of physostigmine, and showed dose-and time-dependent eects. The results suggest that physostigmine may reverse the scopolamine-induced changes in both qEEG and cognitive function. This reversal was temporary and of short duration. #

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Section: Discussionsupporting

confidence: 61%

“…0 mg physostigmine was administered together with 0 . 5 mg scopolamine s.c. (Wesnes et al, 1991). Indeed, in the present study the eects of physostigmine were not evaluated on their own.…”

Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Effects of physostigmine on scopolamine-induced changes in quantitative electroencephalogram and cognitive performance

Ebert

Oertel

Wesnes³

et al. 1998

Hum. Psychopharmacol. Clin. Exp.

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“…Physostigmine, an acetylcholinesterase inhibitor, directly mediates cholinergic function and has been found to improve performance on a variety of cognitive tasks (e.g., Beninger et al 1995;Ormerod and Beninger 2002;Wesnes et al 1991). In the peak procedure, for example, Abner et al (2001) found reduced variability in the time to stop responding (better temporal precision) in mice.…”

Section: Introductionmentioning

confidence: 97%

Pharmacological manipulations of interval timing using the peak procedure in male C3H mice

et al. 2008

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“…Systemic administration of the nonselective muscarinic receptor antagonists atropine and scopolamine causes cognitive deficits in humans (Christensen et al, 1992;Ebert and Kirch, 1998;Wesnes et al, 1991), nonhuman primates (Rupniak et al, 1989) and rodents (Patel and Tariot, 1991;Sunderland et al, 1986). In human volunteers, the pattern of cognitive impairment caused by scopolamine mimics in some aspects the cognitive symptomology seen in Alzheimer's disease (AD) (Ebert and Kirch, 1998) which is associated with the degeneration of cholinergic neurons in the basal forebrain resulting in a reduction of cholinergic neurotransmission in the forebrain (Araujo et al, 1988;DeKosky et al, 1996;Kuhl et al, 1999;Shinotoh et al, 2000;Shiozaki et al, 1999;Whitehouse et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

Selective 5-HT1A Antagonists WAY 100635 and NAD-299 Attenuate the Impairment of Passive Avoidance Caused by Scopolamine in the Rat

Misane

Ögren

2003

Neuropsychopharmacol

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Systemic administration of the muscarinic-receptor antagonists atropine and scopolamine produces cognitive deficits in humans, nonhuman primates and rodents. In humans, these deficits resemble symptoms of dementia seen in Alzheimer's disease. The passive avoidance (PA) task has been one of the most frequently used animal models for studying cholinergic mechanisms in learning and memory. The present study examined the ability of two selective 5-HT 1A receptor antagonists WAY 100635 and NAD-299 (robalzotan) and two acetylcholinesterase (AChE) inhibitors tacrine and donepezil to attenuate the impairment of PA retention caused by the nonselective muscarinic receptor antagonist scopolamine in the rat. Although demonstrating differences in their temporal kinetics, both WAY 100635 and NAD-299 attenuated the impairment of PA caused by scopolamine (0.3 mg/kg s.c.). Donepezil did not block the PA deficit caused by the 0.3 mg/kg dose of scopolamine, but it prevented the inhibitory effects of the 0.2 mg/kg dose of scopolamine. In contrast, tacrine was effective vs both the 0.2 and 0.3 mg/kg doses of scopolamine. These results indicate that (1) a functional 5-HT 1A receptor antagonism can attenuate the anterograde amnesia produced by muscarinic-receptor blockade, and (2) the AChE inhibitors tacrine and donepezil differ in their ability to modify muscarinic-receptor-mediated function in vivo. These results suggest that 5-HT 1A receptor antagonists may have a potential in the treatment of cognitive symptoms in psychopathologies characterized by reduced ACh transmission such as Alzheimer's disease.

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Cholinesterase Inhibition in the Scopolamine Model of Dementia

Cited by 55 publications

References 13 publications

Effects of physostigmine on scopolamine-induced changes in quantitative electroencephalogram and cognitive performance

Effects of physostigmine on scopolamine-induced changes in quantitative electroencephalogram and cognitive performance

Pharmacological manipulations of interval timing using the peak procedure in male C3H mice

Selective 5-HT1A Antagonists WAY 100635 and NAD-299 Attenuate the Impairment of Passive Avoidance Caused by Scopolamine in the Rat

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