Partial reversal of anticholinergic amnesia by choline chloride

doi:10.1016/0024-3205(81)90674-3

Life Sciences

Volume 29, Issue 13, 28 September 1981, Pages 1317-1323

https://doi.org/10.1016/0024-3205(81)90674-3 Get rights and content

Abstract

Twenty young adult males were given tests of memory and mood after receiving choline chloride plus scopolamine, placebo plus scopolamine, and two placebos on separate days in randomized order. Scopolamine caused a marked impairment in performance on a verbal learning task. Pretreatment with choline caused a small but significant decrease in this impairment and partially reversed the mood changes produced by scopolamine. Although several previous studies have failed to demonstrate that choline has a significant effect on cognition when given alone, the present results indicate that choline can enhance cognition under conditions of cholinergic blockade. This is consistent with preclinical data indicating that cholinergic neurons are most sensitive to precursor availability when they are firing rapidly.

References (39)

P. Davies et al.
Lancet
(1976)
N.R. Sims et al.
Lancet
(1980)
D.R. Haubrich et al.
Life Sci.
(1975)
D.R. Haubrich et al.
Life Sci.
(1979)
R.C. Mohs et al.
Psychiat. Res.
(1980)
R.C. Mohs et al.
Neurobiol. of Aging
(1980)
W.D. Boyd et al.
Lancet
(1977)
P. Etienne et al.
Lancet
(1978)
S. Eckernas et al.
Life Sci.
(1980)
B. Milner

L. Wecker et al.

Brain Res.

(1980)

E.K. Perry et al.

Lancet

(1977)

N. Sitaram et al.

Life Sci.

(1978)

D.A. Drachman et al.

Arch. Neurol.

(1974)

J.S. Ketchum et al.

Psychopharmacologia

(1973)

K.L. Davis et al.

Science

(1978)

K.L. Davis et al.

N. Engl. J. Med.

(1979)

D.A. Drachman

Neurology

(1977)

N. Sitaram et al.

Science

(1978)

Cited by (22)

Galanthamine from snowdrop - The development of a modern drug against Alzheimer's disease from local Caucasian knowledge
2004, Journal of Ethnopharmacology
In recent years, galanthamine isolated from several members of the Amaryllidaceae (Leucojum spp., Narcissus species, Galanthus spp.) has become an important therapeutic options used to slow down the process of neurological degeneration in Alzheimer’s disease. This review traces aspects of the history of its development from little known observational studies in the Caucasus Mountains (Southern Russia), to the use of this drug in Eastern European countries (esp. Bulgaria) in the treatment of poliomyelitis and ultimately to the recent introduction onto Western markets in the treatment of Alzheimer’s disease. Of note, little is known about the early history of the drug’s development and the review also points to other gaps in our knowledge about the ethnopharmacology, pharmacology and clinical use of galanthamine.
Increased cognitive sensitivity to scopolamine with age and a perspective on the scopolamine model
1992, Brain Research Reviews
18 older normal volunteers (mean age = 66.5 ± 7.9 years) and 46 younger volunteers (mean age = 27.0 ± 6.1 years) were administered the anticholinergic drug scopolamine (0.5 mg i.v.) followed by a battery of cognitive tests evaluating attention, learning and memory. The older subjects were significantly more impaired than the younger by scopolamine on some tests of learning and memory. This increased sensitivity of the older group to scopolamine is consistent with studies in animals and humans showing decreased cholinergic system function with age. The findings also indicate that age is an important variable to consider in using the scopolamine model of memory impairment. The cognitive impairment caused by scopolamine in younger subjects in this and prior studies is similar to some, but not all aspects of the impairment which occurs in normal aging^11,29,37. Scopolamine also caused impairments on digit span and word fluency tasks, which are not consistent with normal aging changes. In the older group of subjects, scopolamine produced aspects of the cognitive impairment which occurs in AD on tests of episodic memory and learning, vigilance-attention, category retrieval, digit span, and number of intrusions^64,86,88,91. Other areas of cognition that are of relevence to aging and AD such as psychomotor speed, praxis, concept formation and remote memory were not evaluated in this study. Some of these are being evaluated in ongoing studies, along with additional and more specific tests of retrieval from knowledge memory, implicit memory and attention. The scopolamine model has provided a fruitful pharmacologie starting point for the study of a number of cognitive operations. The idea of dissecting apart aspects of memory systems pharmacologically depends on the availability of neurochemically specific drugs and on the specificity and sensitivity of neuropsychological tests for distinct cognitive operations or domains. Further studies using such tools will aid not only in the understanding of the impairments which occur in aging and in AD, but also of the conceptualization of memory and other cognitive operations and ultimately the physiological mechanisms involved in memory and learning.
A threshold for the protective effect of over-reinforced passive avoidance against scopolamine-induced amnesia
1992, Behavioral and Neural Biology
Acetylcholine-receptor blockers produce amnesia of aversively motivated behaviors. However, when animals are submitted to relatively high intensities of footshock (over-reinforcement), anticholinergic treatment does not induce memory impairments. The aim of this work was to determine whether the antiamnesic effect produced by increasing the magnitude of the negative reinforcer is gradually established or if a threshold should be reached to obtain such an effect. Wistar rats were trained in passive avoidance using 2.5, 2.6, 2.7, 2.8, 2.9 or 3.0 mA; 5 min after training they were given one systemic injection of scopolamine (8 mg/kg). An amnesic state was produced in the groups that were trained with the lower intensities (2.5–2.7 mA); with the three higher intensities near-perfect retention was evident. These results suggest that acetylcholine is critically involved in memory consolidation, and that by increasing the magnitude of the negative reinforcer, a threshold is reached where cholinergic activity of the nervous system is not necessary for the development of the consolidation process.
Is acetylcholine involved in memory consolidation of over-reinforced learning?
1990, Brain Research Bulletin
Systemic administration of anticholinergic drugs produces amnesia. To determine whether this effect can be prevented by increasing the magnitude of the learning experience, independent groups of rats were trained in passive avoidance, using a 3.0-mA footshock, and then injected with scopolamine (2, 4, 6, 8 or 12 mg/kg). When retention of the task was evaluated, a dose-dependent amnesic effect was found. When footshock intensity was increased to 6.0 and 9.0 mA, injections of 8 and 12 mg/kg of scopolamine did not produce memory impairments. These findings indicate that acetylcholine plays an important role in consolidation of passive avoidance, but it does not seem to be involved in memory processes when the magnitude of the negative reinforcer is increased.
Cognitive enhancers: Potential strategies and experimental results
1989, Progress in Neuropsychopharmacology and Biological Psychiatry
Wenk, Gary L. and David S. Olton: Cognitive Enhancers: Potential Strategies and Experimental Results. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1989, $13$ (Suppl): S117–S139
- 1.
  1. Cognitive impairments follow natural processes such as aging, diseases, exposure to neurotoxins and traumatic injury. In all of these instances, the brain possesses some capability for recovery.
- 2.
  2. A cognitive enhancer is any compound that will help this recovery occur more rapidly, or increase the final level of performance.
- 3.
  3. This chapter describes the types of strategies that can be used to develop a cognitive enhancer with emphasis on studies of the cholinergic system.
Pharmacologic modelling of Alzheimer's disease
1986, Progress in Neuropsychopharmacology and Biological Psychiatry
Sunderland, Trey, Pierre N. Tariot, Herbert Weingartner, Dennis L. Murphy, Paul A. Newhouse, Edward A. Mueller and Robert M. Cohen: Pharmacologie modelling of Alzheimer's disease. Prog. Neuro-Psychopharmacol. and Biol. Psychiat. 1986, $10$ (3–5): 599–610.
- 1.
  1. Evidence pointing to the central role of the cholinergic system in normal human memory function and disorders such as Alzheiner's disease has grown tremendously in recent years.
- 2.
  2. Anticholinergic and non-cholinergic agents have been found to create transient, memory impairments in young adults which mimic the changes asociated with normal aging or amnesia.
- 3.
  3. The rationale for using scopolamine, a centrally active anticholinergic agent, as a pharmacologie probe of memory function is reviewed using data from studies in animals and humans.
- 4.
  4. The cognitive functioning of normal elderly controls given scopolamine is compared to the baseline functioning of patients with Alzheiner's disease, followed by a discussion of the use of scopolamine as a modelling agent for dementia.

View all citing articles on Scopus

View full text

Partial reversal of anticholinergic amnesia by choline chloride

Abstract

Lancet

Lancet

Life Sci.

Life Sci.

Psychiat. Res.

Neurobiol. of Aging

Lancet

Lancet

Life Sci.

Brain Res.

Lancet

Life Sci.

Arch. Neurol.

Psychopharmacologia

Science

N. Engl. J. Med.

Neurology

Science