The scopolamine-reversal paradigm in rats and monkeys

The importance of computer-assisted operant-conditioning memory tasks for screening drug candidates

Jerry J. Buccafusco, Alvin V Terry, Scott J. Webster, Daniel Martin, Elizabeth J. Hohnadel, Kristy A. Bouchard, Samantha E. Warner

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)481-494
Number of pages14
JournalPsychopharmacology
Volume199
Issue number3
DOIs
StatePublished - Aug 1 2008

Fingerprint

Operant Conditioning
Preclinical Drug Evaluations
Scopolamine Hydrobromide
Haplorhini
Alzheimer Disease
Pharmaceutical Preparations
Cognition
Aptitude
Water
Macaca mulatta
Cholinergic Agents
Primates
Clinical Trials
Pharmacology
Discrimination (Psychology)
donepezil

Keywords

  • Cognition
  • Delayed matching
  • Donepezil
  • Monkeys
  • Scopolamine
  • Spatial memory

ASJC Scopus subject areas

  • Pharmacology

Cite this

The scopolamine-reversal paradigm in rats and monkeys : The importance of computer-assisted operant-conditioning memory tasks for screening drug candidates. / Buccafusco, Jerry J.; Terry, Alvin V; Webster, Scott J.; Martin, Daniel; Hohnadel, Elizabeth J.; Bouchard, Kristy A.; Warner, Samantha E.

In: Psychopharmacology, Vol. 199, No. 3, 01.08.2008, p. 481-494.

Research output: Contribution to journalArticle

Buccafusco, Jerry J. ; Terry, Alvin V ; Webster, Scott J. ; Martin, Daniel ; Hohnadel, Elizabeth J. ; Bouchard, Kristy A. ; Warner, Samantha E. / The scopolamine-reversal paradigm in rats and monkeys : The importance of computer-assisted operant-conditioning memory tasks for screening drug candidates. In: Psychopharmacology. 2008 ; Vol. 199, No. 3. pp. 481-494.
@article{1f568906c18a49e7bebd67bed434654f,
title = "The scopolamine-reversal paradigm in rats and monkeys: The importance of computer-assisted operant-conditioning memory tasks for screening drug candidates",
abstract = "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.",
keywords = "Cognition, Delayed matching, Donepezil, Monkeys, Scopolamine, Spatial memory",
author = "Buccafusco, {Jerry J.} and Terry, {Alvin V} and Webster, {Scott J.} and Daniel Martin and Hohnadel, {Elizabeth J.} and Bouchard, {Kristy A.} and Warner, {Samantha E.}",
year = "2008",
month = "8",
day = "1",
doi = "10.1007/s00213-007-0887-8",
language = "English (US)",
volume = "199",
pages = "481--494",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - The scopolamine-reversal paradigm in rats and monkeys

T2 - The importance of computer-assisted operant-conditioning memory tasks for screening drug candidates

AU - Buccafusco, Jerry J.

AU - Terry, Alvin V

AU - Webster, Scott J.

AU - Martin, Daniel

AU - Hohnadel, Elizabeth J.

AU - Bouchard, Kristy A.

AU - Warner, Samantha E.

PY - 2008/8/1

Y1 - 2008/8/1

N2 - 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.

AB - 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.

KW - Cognition

KW - Delayed matching

KW - Donepezil

KW - Monkeys

KW - Scopolamine

KW - Spatial memory

UR - http://www.scopus.com/inward/record.url?scp=46649086754&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=46649086754&partnerID=8YFLogxK

U2 - 10.1007/s00213-007-0887-8

DO - 10.1007/s00213-007-0887-8

M3 - Article

VL - 199

SP - 481

EP - 494

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

IS - 3

ER -