Scopolamine alters rhesus monkey performance on a novel neuropsychological test battery

Taffe, Michael A.; Weed, Michael R.; Gold, Lisa

doi:10.1016/s0926-6410(99)00021-x

Cited by 81 publications

(72 citation statements)

References 41 publications

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“…Some of the controversy clearly has been related to the types of tests administered, the age or disease status of the subjects, and the dose of scopolamine. Our results in monkeys differ to a small degree from those reported by Taffe et al 1999 who studied the effects of scopolamine in a computer-presented delayed non-matching-to-sample task. In that study, the scopolamine-induced impairment of task accuracy was reported to be delay independent.…”

Section: Discussioncontrasting

confidence: 99%

“…Amnestic agents such as the muscarinic receptor antagonists atropine and scopolamine have been used for decades in experimental animals to induce impairment in their performance of a variety of tasks requiring intact working and reference memory (for review, see Heise 1984;Bartus et al 1987;Taffe et al 1999). Scopolamine had been put to similar use in clinical studies more than 30 years ago (e.g., Drachman and Leavitt 1974).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussioncontrasting

confidence: 99%

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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“…These results are consistent with studies showing that scopolamine impairs encoding for long-term memory in both humans (Ghoneim and Mewaldt, 1977;Rosier et al, 1998;Sherman et al, 2003;Atri et al, 2004) and monkeys (Penetar and McDonough, 1983;Aigner and Mishkin, 1986;Aigner et al, 1991;Tang et al, 1997;Taffe et al, 1999). The changes in parahippocampal activation shown here are consistent with evidence that encoding is impaired by direct infusions of scopolamine into the perirhinal cortex, but not inferotemporal cortex or the dentate gyrus (Tang et al, 1997), and are consistent with monkey lesion studies that have established a role for the PRC in recognition memory (Meunier et al, 1993(Meunier et al, , 1996Baxter and Murray, 2001).…”

Section: Relationship To Behavioral Studiessupporting

confidence: 92%

Scopolamine Reduces Persistent Activity Related to Long-Term Encoding in the Parahippocampal Gyrus during Delayed Matching in Humans

Schön

Atri²,

Hasselmo³

et al. 2005

J. Neurosci.

119

117

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Recent computational modeling and slice physiology studies have suggested that long-term encoding may depend on sustained spiking during brief memory delays in parahippocampal neurons, and that this persistent spiking activity is modulated by effects of acetylcholine at muscarinic receptors. Our recent functional magnetic resonance imaging (fMRI) study has shown that sustained parahippocampal delay period activity during delayed match-to-sample performance in healthy young individuals predicted subsequent memory of visual stimuli on a recognition memory assessment 20 min later (Schon et al., 2004). The current study combined this fMRI paradigm with a pharmacological manipulation to test whether this long-term encoding-related delay activity is reduced in subjects who receive the muscarinic cholinergic antagonist scopolamine before fMRI scanning. Subsequent memory was predicted by sustained activity during brief memory delays bilaterally in the perirhinal/entorhinal cortex, in the right posterior parahippocampal and mid-fusiform gyri, and in the hippocampal body in healthy young individuals without a scopolamine challenge. This activity was reduced in subjects receiving scopolamine. The results are consistent with computational modeling data and behavioral pharmacological studies, suggesting that long-term encoding-related activity may be reduced if cholinergic receptors are blocked by scopolamine.

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“…DNMS choice accuracy was consistently less than perfect in the simultaneous condition, an observation that is consistent with all groups of animals trained in the lab on this task (e.g. Taffe et al (1999); Weed et al (1999)), as well as the delayed matching to sample variant (unpublished observations). Similarly, there was no significant effect of retention interval on choice accu- Mean performance of the MDMA-treated (N ϭ 3) and the vehicle-treated (N ϭ 3) groups on each of the behavioral tasks is summarized.…”

Section: Behaviorsupporting

confidence: 75%

Functional Consequences of Repeated (±)3,4-Methylenedioxymethamphetamine (MDMA) Treatment in Rhesus Monkeys

Taffe

Weed

Davis

et al. 2001

Neuropsychopharmacology

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Six rhesus monkeys were trained to stable performance on neuropsychological tests of memory, reinforcer efficacy, reaction time and bimanual motor coordination. Three monkeys were then exposed to a high-dose, short course regimen of ( Ϯ )3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") (4 days, 10 mg/kg i.m., b.i.d.) Recreational use of the psychoactive drug ( Ϯ )3,4,-methylenedioxymethamphetamine (MDMA) has become increasingly popular over the past two decades (Peroutka 1987;Schuster et al. 1998). Although early studies focused on adverse physiological (e.g., hypertension, hyperthermia, hyponatraemia) or psychiatric (mood disorder, aggression) symptoms associated with acute and/or chronic MDMA exposure, recent evidence suggests that chronic MDMA use may also result in lasting disruption of cognitive function. A number of studies have shown that experienced, abstinent MDMA users are impaired on various tests of memory function (Bolla et al. 1998;Curran and Travill 1997;Krystal et al. 1992;Morgan 1999;, even when compared with users of other recreational drugs. The lasting functional effects of MDMA use may be relatively specific to mnemonic processing, since a number of studies have reported that MDMA users who are impaired on memory tasks exhibit normal performance on tests of reaction time, vigilance or selective attention (Krystal et al. 1992;Vollenweider et al. 1998). Additional evidence suggests that the degree of memory impairment in the MDMA user is positively correlated with the number of cumulative exposures to MDMA (Bolla et al. 1998;Parrott and Lasky 1998). Finally, recent studies have demonstrated that electroencephalographic and metabolic (PET) measures of brain function are altered in MDMA users (Dafters et al. 1999;

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Scopolamine alters rhesus monkey performance on a novel neuropsychological test battery

Cited by 81 publications

References 41 publications

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

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

Scopolamine Reduces Persistent Activity Related to Long-Term Encoding in the Parahippocampal Gyrus during Delayed Matching in Humans

Functional Consequences of Repeated (±)3,4-Methylenedioxymethamphetamine (MDMA) Treatment in Rhesus Monkeys

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