Dose-specific effects of scopolamine on canine cognition: impairment of visuospatial memory, but not visuospatial discrimination.
BACKGROUND
The cholinergic system is linked extensively to memory, but its exact role remains controversial. In particular, scopolamine-induced impairment in rodents is not task specific, which may be due to difficulty in developing rodent protocols to assess deficits in recent memory, in which the remembered event is brief and distinct, and/or to non-specific behavioral impairment.


OBJECTIVE
The present study sought to determine whether scopolamine-induced deficits in recent memory, using a working memory task, could be dose-specifically dissociated from deficits in associative memory in dogs.


METHODS
A Latin-square design was used to determine the effect of scopolamine (5, 10 and 15 microg/kg; SC) on a variable delayed-non-matching-to-position (DNMP) task, which assesses visuospatial working memory. Subsequently, the minimal effective dose (15 microg/kg; SC) was administered prior to testing on a landmark discrimination task, which provides a measure of allocentric spatial ability, a black-white discrimination task, an oddity discrimination task and tests of exploratory behavior. We also investigated the effects of a 30 microg/kg dose (SC) on tests of oddity discrimination and behavioral activity.


RESULTS
A 15 microg/kg dose produced significant impairment on the DNMP task, but did not affect performance of any discrimination task and did not alter behavior on tests of open field or curiosity. A 30 microg/kg dose caused disruption on discrimination performance and on open field measures.


CONCLUSIONS
Working memory performance is most sensitive to scopolamine-induced impairment and can be dissociated from scopolamine-induced deficits in discrimination performance and non-cognitive behaviors. The present results indicate that scopolamine-induced impairments of working memory in the dog can serve as a model of age-related cholinergic dysfunction.
Araujo
J A
JA
Department of Pharmacology, University of Toronto, 1 King's College Circle, M5S 1A8, Toronto, ON, Canada.
Chan
A D F
AD
Winka
L L
LL
Seymour
P A
PA
Milgram
N W
NW
D000375:Aging / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects*; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000523:psychology; D018727:Muscarinic Antagonists / Q000008:administration & dosage; D012201:Reward; D012601:Scopolamine / Q000008:administration & dosage; D014786:Vision Disorders / Q000139:chemically induced* / Q000523:psychology
D018727:Muscarinic Antagonists; D012601:Scopolamine