Scopolamine induced deficits in a battery of rat cognitive tests: comparisons of sensitivity and specificity.
Despite much research, the cognitive effects of scopolamine hydrobromide, a cholinergic antagonist, remain controversial. Scopolamine affects multiple systems each of which can impact behavior. One way to tease apart the effects of the drug is to determine the effects of low scopolamine doses on different abilities. The present experiments compared the effects of low doses of scopolamine on a single group of rats conducting a battery of behavioral tasks: Morris water maze, radial arm maze, delayed non-matching to position tasks, and fixed ratio 5 bar pressing. The behavioral battery ranged from tasks having little cognitive demand to those thought to be based more on attention and spatial-working memory. Control experiments using additional groups of rats assessing peripheral versus central effects were conducted with both liquid and dry reinforcement and with methyl scopolamine. Furthermore, the 5-choice serial reaction time test assessed scopolamine effects on attention. The data show a wide spectrum of central and peripheral cholinergic involvement. The central effects include attention and motor initiation, both of which impact and interact with the mnemonic function of acetylcholine. These results show that a limited disruption of the central cholinergic system can have profound effects on attention and/or psychomotor control before any measurable mnemonic disruption.
General Pharmacology-Neuroscience Core, Drug Innovation and Realization, Vertex Pharmaceuticals Inc., Cambridge, Massachusetts 02139, USA. donald_hodges@vrtx.com
Donald Bartholomew
DB
Hodges
Mark D
MD
Lindner
John B
JB
Hogan
Kelly M
KM
Jones
Etan J
EJ
Markus
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001288:Attention / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D018680:Cholinergic Antagonists / Q000009:adverse effects* / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D011939:Mental Recall / Q000187:drug effects; D019832:N-Methylscopolamine / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012601:Scopolamine / Q000009:adverse effects* / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013028:Space Perception / Q000187:drug effects
D018680:Cholinergic Antagonists; D012601:Scopolamine; D000109:Acetylcholine; D019832:N-Methylscopolamine